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The Journal of Immunology, 2000, 164: 2277-2280.
Copyright © 2000 by The American Association of Immunologists

CUTTING EDGE

Cutting Edge: Differential Production of Prostaglandin D2 by Human Helper T Cell Subsets

Kazuya Tanaka*, Kazuyuki Ogawa*, Kazuo Sugamura{dagger}, Masataka Nakamura{ddagger}, Shoichi Takano* and Kinya Nagata1,*

* R & D Center, BioMedical Laboratories, Inc., Kawagoe, Saitama, Japan; {dagger} Department of Microbiology and Immunology, Tohoku University School of Medicine, Sendai, Miyagi, Japan; and {ddagger} Human Gene Sciences Center, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 References
 
Several effector molecules, including cytokines, are differentially produced by Th1 and Th2 cells. We used a gene expression screen method to identify a gene encoding hematopoietic PG D synthase (hPGDS) which was preferentially expressed in human Th2 but not Th1 clones. Studies with anti-hPGDS mAbs confirmed the Th2-dominated expression of hPGDS protein. Upon stimulation with anti-CD3 plus anti-CD28 mAbs, coordinated cyclooxygenase-2 expression and PGD2 production were induced in Th2 lines. hPGDS expression was also observed in a small population (<1.0%) of peripheral blood CD4+ lymphocytes from healthy adults. Most hPGDS-expressing CD4+ lymphocytes showed a typical Th2-type cytokine pattern. Our results suggest that, at the sites of Ag presentation, at least part of the Th2 cell population produces PGD2, which may be involved in various aspects of Th2-related immune responses similar to mast cells.


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 References
 
T helper cells are functionally classified into two major subsets, Th1 and Th2, based on their respective cytokine profiles. In humans, Th1 cells produce IFN-{gamma} which strongly promotes cell-mediated immune responses. Th2 cells typically produce IL-4, IL-5, and IL-13, which promote humoral immunity including IgE, as well as growth and differentiation of mast cells and eosinophils (1). In addition to these characteristic cytokines, a number of proteins have been reported to be differentially expressed between the subsets such as receptors for cytokines and chemokines, adhesion molecules, and transcription factors (2, 3, 4, 5, 6), and they are considered to play important roles in the development, site-specific recruitment, and effector functions of each subset.

Various protein mediators and low m.w. inflammatory mediators such as PGs and leukotrienes are differentially produced and play important roles in diverse inflammatory processes (7). However, differences between Th1 and Th2 cell production of low m.w. inflammatory mediators have not been well examined.

In this study, we present data suggesting that a lipid mediator, PGD2, which is well known as the major prostanoid produced by allergen-provoked mast cells, is also preferentially produced by Ag-stimulated human Th2 but not Th1 cells.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 References
 
Cells

A human T cell line, Jurkat, was cultured as described previously (8). Th1 and Th2 cells were generated from PBMCs of consenting healthy adults and maintained by repeatedly stimulating cells with immobilized OKT3 (Janssen-Kyowa, Tokyo, Japan) every 10–14 days as described previously (8). Th lines (CD4+ cells > 95%) that had been cultured for >7 days after the last stimulation were used in each experiment.

Generation of recombinant hematopoietic PG D synthase (hPGDS)2 and anti-hPGDS mAbs

A full-length hPGDS cDNA (clone E26; 0.8 kb) was excised from a Lambda ZAP II phagemid vector (Stratagene, La Jolla, CA) at the PstI site in the 5' untranslated region of hPGDS cDNA and EcoRI site in the cloning adaptor, and then subcloned into PstI/EcoRI sites of the pcDL-SR{alpha}296 vector (9) (pcDL-SR{alpha}/E26). Jurkat/hPGDS cells were generated by stably transfecting Jurkat cells with pcDL-SR{alpha}/E26. 6xHis-hPGDS, a recombinant protein composed of a histidine hexamer and the entire hPGDS protein, was generated in Escherichia coli using a pQE expression vector system (Qiagen, Valencia, CA), and purified on Ni-nitrilotriacetic acid (Qiagen) and Mono-Q (Amersham Pharmacia Biotech, Uppsala, Sweden) columns. Mouse anti-hPGDS mAbs, AE3C (IgG1) and EBC45 (IgG1), were generated by fusion of SP2/O-Ag8 cells and splenocytes from 6xHis-hPGDS-immunized BALB/c mice.

Western blotting for hPGDS and cyclooxygenase (Cox)-2

Cells were lysed in lysis solution (1% Nonidet P-40, 150 mM NaCl, 50 mM Tris-HCl (pH 7.5), 1 mM PMSF, and 1 µg/ml aprotinin) on ice for 1 h. Cell lysates were centrifuged and then subjected to SDS-PAGE on 7.5% (Cox-2) or 12.5% (hPGDS) polyacrylamide gels under reducing conditions. Ags were transferred onto a nitrocellulose membrane and visualized as described previously (8) using either biotinylated AE3C (5 µg/ml) and peroxidase-conjugated streptavidin (for hPGDS; Vector Laboratories, Burlingame, CA) or goat anti-Cox-2 peptide Ab (2 µg/ml; Santa Cruz Biotechnology, Santa Cruz, CA) and peroxidase-labeled anti-goat Ig (for Cox-2; American Qualex, San Clemente, CA).

Flow cytometric analysis

Reagents used in flow cytometry were described previously (8, 10) except for an allophycocyanin (APC)-conjugated streptavidin (Becton Dickinson, Franklin Lakes, NJ). Surface Ags were stained using the instructions provided by the supplier. Intracellular cytokines and CRTH2 were stained as described previously (8). For detection of hPGDS, cells were fixed in 4% formaldehyde/PBS at room temperature for 5 min, washed, and permeabilized in permeabilizing solution (Becton Dickinson) at room temperature for 10 min. Cells were then stained with biotinylated EBC45 (5 µg/ml) in the presence (control) or absence of 6xHis-hPGDS (10 µg/ml) followed by PE-, RED670-, or APC-labeled streptavidin. Stained cells were analyzed on a FACSCalibur flow cytometer (Becton Dickinson) using CellQuest software (Becton Dickinson).

Assay for PGD2 production

Cells (5 x 106 cells/ml) were incubated in OKT3 (10 µg/ml)-coated 96-well tissue culture plates in the presence of an anti-CD28 mAb KOLT-2 (1 µg/ml) (Nichirei, Tokyo, Japan) for 0.5–12 h. Concentrations of PGD2 in the culture supernatants were measured using a Prostaglandin D2-Mox Enzyme Immunoassay kit (Cayman Chemicals, Ann Arbor, MI).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 References
 
We have previously isolated a number of Th2 clone-specific cDNA fragments by the gene expression screen method (8). Searches of the GenBank database revealed that one such cDNA fragment, designated fragment E (234 bp), corresponds to nt 1–234 of a cDNA clone for human hPGDS (accession number D82073) (11). A full-length hPGDS cDNA (clone E26, 862 bp) containing 600 bp encompassing the entire coding region was isolated from a human Th2 (clone 2P26) cDNA library (8) using the cDNA fragment E as a probe.

Northern and Western blot analyses detected hPGDS mRNA and protein at various levels in Th2 clones, but not in Th1 clones (Fig. 1Go, A and B). Flow cytometric analysis illustrated a substantial population of cells (but not all) in each Th2, but not Th1, line expressed hPGDS (Fig. 1GoD). hPGDS specificity of the staining with EBC45 was corroborated using hPGDS-transfected and untransfected Jurkat cells (Fig. 1GoC).



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  		FIGURE 1. Selective expression of hPGDS mRNA and protein in human Th2 cells. A, Total RNA (10 µg) from Th1 (lanes 1 and 2) and Th2 (lanes 3 and 4) clones were analyzed for relative levels of hPGDS mRNA by Northern blotting using cDNA clone E26 as a probe as described previously (8 ). B, Cell extracts (105 cells equivalent/lane) from Th1 clones, Th2 clones, Jurkat, and Jurkat/hPGDS (lanes 1–4 and 5–10, respectively) were analyzed for hPGDS protein by Western blotting using an anti-hPGDS mAb AE3C. C, Flow cytometric analysis of hPGDS expression in Jurkat and Jurkat/hPGDS stained with EBC45 (solid line) or control Ig (dotted line) followed by PE-labeled anti-mouse Ig (Chemicon, Temecula, CA). D, Cytokine production and hPGDS expression in Th1 (a and c) and Th2 (b and d) lines. In c and d, cells were stained with biotinylated EBC45 in the presence (dotted line) or absence (solid line) of 6xHis-hPGDS. Percentages of positive cells in each gated region are shown in each panel.

 
Upon stimulation, Th2 lines produced a significant amount of PGD2 (Fig. 2GoA). As expected, the production of PGD2 occurred coincidentally with the induction of an upstream enzyme, Cox-2. In several pairs of Th lines, the level of PGD2 production correlated well with the expression level of hPGDS (Fig. 2GoB). Interestingly, Cox-2 was also preferentially induced in Th2-oriented lines for every Th pair (Fig. 2GoB). Expression of Cox-1, an isozyme of Cox-2, was not clearly detected in this study.



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  		FIGURE 2. Cox-2 expression and PGD2 production in Th2 lines. A, Time course of Cox-2 expression and PGD2 production (n = 3) in a representative Th2 line stimulated with OKT3 and KOLT-2. B, Th lines from five healthy donors (a–e), which had been generated under either Th1- or Th2-oriented culture conditions (culture condition 1 or 2, respectively) as described previously (8 ), were stimulated with OKT3 and KOLT-2 for 6 h, and then the levels of PGD2 (n = 3), Cox-2, and hPGDS in the cultures were examined. Proportions (%) of Th1 and Th2 cells in each Th line, which were determined by flow cytometry (8 ), are presented.

 
We next examined hPGDS expression in fresh peripheral blood leukocytes from several healthy adults by flow cytometric analysis. On side and forward light scatter analysis, hPGDS-expressing cells were found in the lymphocyte/lymphoblast region, but not in the monocyte and granulocyte regions (data not shown). In the lymphocyte/lymphoblast region, hPGDS expression was distinctly observed in a small population (<1%) of both CD4+ lymphocytes and unidentified CD3- cells, and weakly in most Fc{epsilon}RI+ cells which were probably basophils (12) (Fig. 3GoA). For all donors, hPGDS-expressing CD4+ lymphocytes showed the phenotype characteristic of recently activated effector/memory T cells (CD25+CD45RA-CD45RO+) and were strongly positive for CRTH2, a Th2-related surface molecule (8) (Fig. 3GoB). They also frequently produced IL-4, but little IFN-{gamma} in response to stimulation with PMA and ionomycin (Fig. 4Go). These results indicated that hPGDS was also expressed in vivo in close association with Th2 but not Th1 cells.



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  		FIGURE 3. hPGDS expression in PBMCs from healthy adults. A, PBMCs from a healthy donor were stained with mAbs to surface markers (abscissa) and then fixed, permeabilized, and stained for intracellular hPGDS (ordinate). Quadrants were set according to the results of control staining (a). Only cells located in the lymphocyte region were analyzed. B, PBMCs from a healthy adult were stained with peridinin chlorophyll protein (PerCP)- (a–c) or FITC (d and e)-labeled anti-CD4 along with the indicated mAbs (abscissa) and then fixed, permeabilized, and stained for hPGDS (ordinate). CD4+ lymphocytes gated by PerCP or FITC staining were analyzed.

 


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  		FIGURE 4. Cytokine production in hPGDS-expressing CD4+ lymphocytes. PBMCs from a healthy donor were stimulated with PMA and ionomycin in the presence of brefeldin A at 37°C for 4 h as described previously (8 ). After incubation, these cells were first stained with PerCP-labeled anti-CD4 and then were fixed, permeabilized, and additionally stained with FITC-conjugated anti-IFN-{gamma}, PE-labeled anti-IL-4, and biotinylated EBC45 and APC-conjugated streptavidin. On lymphocyte population, total CD4+ lymphocytes (region (R) 1), hPGDS- CD4+ lymphocytes (R2), and hPGDS+ CD4+ lymphocytes (R3) were gated as shown in b. Then cytokine patterns of cells in each gated region were analyzed (c and f for R1, d and g for R2, and e and h for R3). Results of control stainings for hPGDS and cytokines are shown in a and c–e. Similar results were obtained with three other healthy donors.

 

   Discussion
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
References
 
PGD2 has been shown to play various physiological and pathophysiological functions such as sleep promotion, inhibition of platelet aggregation, relaxation of smooth muscles, vasodilation, and bronchoconstriction (13). PGD2 is formed from arachidonic acid by successive enzyme reactions. In stimulated cells, Cox-1 and/or Cox-2 transform arachidonic acid into PGH2, a common precursor of PGs. Subsequently, if present, prostaglandin D synthase (PGDS) converts PGH2 into PGD2 (14, 15). Two types of PGDS have been identified: glutathione-independent, lipocalin-type PGDS (brain PGDS) and glutathione-dependent PGDS (hPGDS) (14). hPGDS is expressed on mast cells from various tissues and on certain macrophage-lineage cells such as histiocytes, dendritic cells, Kupffer cells, and Langerhans cells in vivo (16, 17).

Our study revealed for the first time that some Th2 but not Th1 cells in vitro also express hPGDS and can produce PGD2 in response to a stimulus mimicking Ag stimulation. We then demonstrated that a significant subpopulation of Th2- but not Th1-type cells in normal peripheral blood actually express hPGDS. Recent studies have demonstrated that normal blood T cells constitutively express Cox-1 and inducibly express Cox-2 (18). Therefore, along with our in vitro finding, it is most likely that hPGDS-expressing Th2-type cells in vivo can produce PGD2 in response to antigenic stimulation, although direct confirmation is required.

Mast cells are known to be the major producers of PGD2. However, the present study demonstrated that the levels of PGD2 produced by Th2 lines were physiologically significant and, in some cases, comparable to those produced by mast cells (19). Furthermore, it is conceivable that, according to the sites and the time of Ag presentation, some Th2 cells may release PGD2 in spatially and temporally different phases than do mast cells.

PGE2, an another product of Cox, is well known to shift the immune response toward a Th2 phenotype by elevating intracellular cAMP (20). PGD2 also induces the generation of cAMP in PBL, but, in the literature, its effect on the Th1/Th2 balance is not remarkable (21, 22). However, PGD2 has been demonstrated to have multiple effects on the immune system, such as enhancement of mediator release and induction of chemokinesis in eosinophils, inhibition of superoxide generation in neutrophils, and suppression of T cell mitogenesis (21, 23, 24, 25). Most recently, PGD2 has also been shown to have anti-inflammatory properties in carrageenin-induced pleurisy (26).

Thus, through the production of PGD2 in addition to cytokines, Th2 cells may participate in more diverse aspects of Th2-mediated immune reactions than have previously been considered. Th2 cells, along with eosinophils and basophils, have been shown to accumulate into the sites of allergic inflammation (27, 28). Whether hPGDS-expressing Th2 cells actually increase in such sites or not is one of the next questions to be addressed in future studies.


   Acknowledgments
 
We thank Dr. Y. Takebe (National Institute of Infectious Disease, Tokyo, Japan) for the expression vector pcDL-SR{alpha}296.


   Footnotes
 
1 Address correspondence and reprint requests to Dr. Kinya Nagata, R & D Center, BioMedical Laboratories, Inc., 1361-1 Matoba, Kawagoe, Saitama 350-1101, Japan. E-mail address: Back

2 Abbreviations used in this paper: hPGDS, hematopoietic PG D synthase; PGDS, prostaglandin D synthase; PerCP, peridinin chlorophyll protein; APC, allophycocyanin; Cox, cyclooxygenase. Back

Received for publication November 11, 1999. Accepted for publication December 27, 1999.


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 References
 

  1. Abbas, A. K., K. M. Murphy, A. Sher. 1996. Functional diversity of helper T lymphocytes. Nature 383:787.[Medline]
  2. Bach, E. A., S. J. Szabo, A. S. Dighe, A. Ashkenazi, M. Aguet, K. M. Murphy, R. D. Schreiber. 1995. Ligand-induced autoregulation of IFN-{gamma} receptor ß chain expression in T helper cell subsets. Science 270:1215.[Abstract/Free Full Text]
  3. Rogge, L., L. Barberis-Maino, M. Biffi, N. Passini, D. H. Presky, U. Gubler, F. Sinigaglia. 1997. Selective expression of an interleukin-12 receptor component by human T helper 1 cells. J. Exp. Med. 185:825.[Abstract/Free Full Text]
  4. Sallusto, F., A. Lanzavecchia, C. R. Mackay. 1998. Chemokines and chemokine receptors in T-cell priming and Th1/Th2- mediated responses. Immunol. Today 19:568.[Medline]
  5. Austrup, F., D. Vestweber, E. Borges, M. Löhning, R. Bräuer, U. Herz, H. Renz, R. Hallmann, A. Scheffold, A. Radbruch, A. Hamann. 1997. P- and E-selectin mediate recruitment of T-helper-1 but not T-helper-2 cells into inflamed tissues. Nature 385:81.[Medline]
  6. Zheng, W., R. A. Flavell. 1997. The transcription factor GATA-3 is necessary and sufficient for Th2 cytokine gene expression in CD4 T cells. Cell 89:587.[Medline]
  7. Larsen, G. L., P. M. Henson. 1983. Mediators of inflammation. Annu. Rev. Immunol. 1:335.[Medline]
  8. Nagata, K., K. Tanaka, K. Ogawa, K. Kemmotsu, T. Imai, O. Yoshie, H. Abe, K. Tada, M. Nakamura, K. Sugamura, S. Takano. 1999. Selective expression of a novel surface molecule by human Th2 cells in vivo. J. Immunol. 162:1278.[Abstract/Free Full Text]
  9. Takebe, Y., M. Seiki, J. Fujisawa, P. Hoy, K. Yokota, K. Arai, M. Yoshida, N. Arai. 1988. SR{alpha} promoter: an efficient and versatile mammalian cDNA expression system composed of the simian virus 40 early promoter and the R-U5 segment of human T-cell leukemia virus type 1 long terminal repeat. Mol. Cell. Biol. 8:466.[Abstract/Free Full Text]
  10. Nagata, K., H. Hirai, K. Tanaka, K. Ogawa, T. Aso, K. Sugamura, M. Nakamura, S. Takano. 1999. CRTH2, an orphan receptor of T-helper-2-cells, is expressed on basophils and eosinophils and responds to mast cell-derived factor(s). FEBS Lett. 459:195.[Medline]
  11. Mahmud, I., N. Ueda, H. Yamaguchi, R. Yamashita, S. Yamamoto, Y. Kanaoka, Y. Urade, O. Hayaishi. 1997. Prostaglandin D synthase in human megakaryoblastic cells. J. Biol. Chem. 272:28263.[Abstract/Free Full Text]
  12. Gane, P., C. Pecquet, P. Lambin, N. Abuaf, F. Leynadier, P. Rouger. 1993. Flow cytometric evaluation of human basophils. Cytometry 14:344.[Medline]
  13. Giles, H., P. Leff. 1988. The biology and pharmacology of PGD2. Prostaglandins 35:277.[Medline]
  14. Ito, S., S. Narumiya, O. Hayaishi. 1989. Prostaglandin D2: a biochemical perspective. Prostaglandins Leukotrienes Essent. Fatty Acids 37:219.[Medline]
  15. Smith, W. L., L. J. Marnett, D. L. DeWitt. 1991. Prostaglandin and thromboxane biosynthesis. Pharmacol. Ther. 49:153.[Medline]
  16. Urade, Y., M. Ujihara, Y. Horiguchi, M. Igarashi, A. Nagata, K. Ikai, O. Hayaishi. 1990. Mast cells contain spleen-type prostaglandin D synthetase. J. Biol. Chem. 265:371.[Abstract/Free Full Text]
  17. Urade, Y., M. Ujihara, Y. Horiguchi, K. Ikai, O. Hayaishi. 1989. The major source of endogenous prostaglandin D2 production is likely antigen-presenting cells: localization of glutathione-requiring prostaglandin D synthetase in histiocytes, dendritic, and Kupffer cells in various rat tissues. J. Immunol. 143:2982.[Abstract]
  18. Iniguez, M. A., C. Punzon, M. Fresno. 1999. Induction of cyclooxygenase-2 on activated T lymphocytes: regulation of T cell activation by cyclooxygenase-2 inhibitors. J. Immunol. 163:111.[Abstract/Free Full Text]
  19. Moon, T. C., M. Murakami, M. D. Ashraf, I. Kudo, H. W. Chang. 1998. Regulation of cyclooxygenase-2 and endogenous cytokine expression by bacterial lipopolysaccharide that acts in synergy with c-kit ligand and Fc{epsilon} receptor I crosslinking in cultured mast cells. Cell. Immunol. 185:146.[Medline]
  20. Snijdewint, F. G., P. Kalinski, E. A. Wierenga, J. D. Bos, M. L. Kapsenberg. 1993. Prostaglandin E2 differentially modulates cytokine secretion profiles of human T helper lymphocytes. J. Immunol. 150:5321.[Abstract]
  21. Burchiel, S. W.. 1979. PGI2 and PGD2 effects on cyclic AMP and human T-cell mitogenesis. Prostaglandins Med. 3:315.[Medline]
  22. Parker, C. W., M. G. Huber, S. M. Godt. 1995. Modulation of IL-4 production in murine spleen cells by prostaglandins. Cell. Immunol. 160:278.[Medline]
  23. Raible, D. G., E. S. Schulman, J. DiMuzio, R. Cardillo, T. J. Post. 1992. Mast cell mediators prostaglandin-D2 and histamine activate human eosinophils. J. Immunol. 148:3536.[Abstract]
  24. Goetzl, E. J.. 1981. The unique role of monohydroxyeicosatetraenoic acids (HETE) in the regulation of eosinophil function. ed. The Eosinophil in Health and Disease 167.-184. Grune and Stratton, New York.
  25. Kanamori, Y., M. Niwa, K. Kohno, L. Y. Al-Essa, H. Matsuno, O. Kozawa, T. Uematsu. 1997. Migration of neutrophils from blood to tissue: alteration of modulatory effects of prostanoid on superoxide generation in rabbits and humans. Life Sci. 60:1407.[Medline]
  26. Gilroy, D. W., P. R. Colville-Nash, D. Willis, J. Chivers, M. J. Paul-Clark, D. A. Willoughby. 1999. Inducible cyclooxygenase may have anti-inflammatory properties. Nat. Med. 5:698.[Medline]
  27. Charlesworth, E. N., A. F. Hood, N. A. Soter, A. Kagey-Sobotka, P. S. Norman, L. M. Lichtenstein. 1989. Cutaneous late-phase response to allergen. Mediator release and inflammatory cell infiltration. J. Clin. Invest. 83:1519.
  28. Robinson, D. S., Q. Hamid, S. Ying, A. Tsicopoulos, J. Barkans, A. M. Bentley, C. Corrigan, S. R. Durham, A. B. Kay. 1992. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N. Engl. J. Med. 326:298.[Abstract]



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Home page
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H. Sasaki, I. Nishikata, T. Shiraga, E. Akamatsu, T. Fukami, T. Hidaka, Y. Kubuki, A. Okayama, K. Hamada, H. Okabe, et al.
Overexpression of a cell adhesion molecule, TSLC1, as a possible molecular marker for acute-type adult T-cell leukemia
Blood, February 1, 2005; 105(3): 1204 - 1213.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
R. Cunard, Y. Eto, J. T. Muljadi, C. K. Glass, C. J. Kelly, and M. Ricote
Repression of IFN-{gamma} Expression by Peroxisome Proliferator-Activated Receptor {gamma}
J. Immunol., June 15, 2004; 172(12): 7530 - 7536.
[Abstract] [Full Text] [PDF]

Home page
 ThoraxHome page
G Bochenek, E Nizankowska, A Gielicz, M Swierczynska, and A Szczeklik
Plasma 9{alpha},11{beta}-PGF2, a PGD2 metabolite, as a sensitive marker of mast cell activation by allergen in bronchial asthma
Thorax, June 1, 2004; 59(6): 459 - 464.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Hammad, H. Jan de Heer, T. Soullie, H. C. Hoogsteden, F. Trottein, and B. N. Lambrecht
Prostaglandin D2 Inhibits Airway Dendritic Cell Migration and Function in Steady State Conditions by Selective Activation of the D Prostanoid Receptor 1
J. Immunol., October 15, 2003; 171(8): 3936 - 3940.
[Abstract] [Full Text] [PDF]

Home page
 GutHome page
S Futagami, T Hiratsuka, A Tatsuguchi, K Suzuki, M Kusunoki, Y Shinji, K Shinoki, T Iizumi, T Akamatsu, H Nishigaki, et al.
Monocyte chemoattractant protein 1 (MCP-1) released from Helicobacter pylori stimulated gastric epithelial cells induces cyclooxygenase 2 expression and activation in T cells
Gut, September 1, 2003; 52(9): 1257 - 1264.
[Abstract] [Full Text]

Home page
 Proc. Natl. Acad. Sci. USAHome page
R. Pedotti, J. J. DeVoss, S. Youssef, D. Mitchell, J. Wedemeyer, R. Madanat, H. Garren, P. Fontoura, M. Tsai, S. J. Galli, et al.
Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination
PNAS, February 18, 2003; 100(4): 1867 - 1872.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
G. Monneret, C. Cossette, S. Gravel, J. Rokach, and W. S. Powell
15R-Methyl-Prostaglandin D2 Is a Potent and Selective CRTH2/DP2 Receptor Agonist in Human Eosinophils
J. Pharmacol. Exp. Ther., January 1, 2003; 304(1): 349 - 355.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
T. Kohyama, T. A. Wyatt, X. Liu, F.-Q. Wen, T. Kobayashi, Q. Fang, H. J. Kim, and S. I. Rennard
PGD2 Modulates Fibroblast-Mediated Native Collagen Gel Contraction
Am. J. Respir. Cell Mol. Biol., September 1, 2002; 27(3): 375 - 381.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
C. Ward, I. Dransfield, J. Murray, S. N. Farrow, C. Haslett, and A. G. Rossi
Prostaglandin D2 and Its Metabolites Induce Caspase-Dependent Granulocyte Apoptosis That Is Mediated Via Inhibition of I{kappa}B{alpha} Degradation Using a Peroxisome Proliferator-Activated Receptor-{gamma}-Independent Mechanism
J. Immunol., June 15, 2002; 168(12): 6232 - 6243.
[Abstract] [Full Text] [PDF]

Home page
 Mol Hum ReprodHome page
T. Michimata, H. Tsuda, M. Sakai, M. Fujimura, K. Nagata, M. Nakamura, and S. Saito
Accumulation of CRTH2-positive T-helper 2 and T-cytotoxic 2 cells at implantation sites of human decidua in a prostaglandin D2-mediated manner
Mol. Hum. Reprod., February 1, 2002; 8(2): 181 - 187.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
Y. Fujitani, Y. Kanaoka, K. Aritake, N. Uodome, K. Okazaki-Hatake, and Y. Urade
Pronounced Eosinophilic Lung Inflammation and Th2 Cytokine Release in Human Lipocalin-Type Prostaglandin D Synthase Transgenic Mice
J. Immunol., January 1, 2002; 168(1): 443 - 449.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
M. L. SEYMOUR, S. RAK, D. ABERG, G. C. RIISE, J. F. PENROSE, Y. KANAOKA, K. F. AUSTEN, S. T. HOLGATE, and A. P. SAMPSON
Leukotriene and Prostanoid Pathway Enzymes in Bronchial Biopsies of Seasonal Allergic Asthmatics
Am. J. Respir. Crit. Care Med., December 1, 2001; 164(11): 2051 - 2056.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
G. Monneret, S. Gravel, M. Diamond, J. Rokach, and W. S. Powell
Prostaglandin D2 is a potent chemoattractant for human eosinophils that acts via a novel DP receptor
Blood, September 15, 2001; 98(6): 1942 - 1948.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
A. Arimura, K. Yasui, J. Kishino, F. Asanuma, H. Hasegawa, S. Kakudo, M. Ohtani, and H. Arita
Prevention of Allergic Inflammation by a Novel Prostaglandin Receptor Antagonist, S-5751
J. Pharmacol. Exp. Ther., August 1, 2001; 298(2): 411 - 419.
[Abstract] [Full Text] [PDF]

Home page
 Int ImmunolHome page
S. Nagai, S.-i. Hashimoto, T. Yamashita, N. Toyoda, T. Satoh, T. Suzuki, and K. Matsushima
Comprehensive gene expression profile of human activated Th1- and Th2-polarized cells
Int. Immunol., March 1, 2001; 13(3): 367 - 376.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Fujimori, Y. Kanaoka, Y. Sakaguchi, and Y. Urade
Transcriptional Activation of the Human Hematopoietic Prostaglandin D Synthase Gene in Megakaryoblastic Cells. ROLES OF THE Oct-1 ELEMENT IN THE 5'-FLANKING REGION AND THE AP-2 ELEMENT IN THE UNTRANSLATED EXON 1
J. Biol. Chem., December 15, 2000; 275(51): 40511 - 40516.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
I-C. Ho, J. P. Arm, C. O. Bingham III, A. Choi, K. F. Austen, and L. H. Glimcher
A Novel Group of Phospholipase A2s Preferentially Expressed in Type 2 Helper T Cells
J. Biol. Chem., May 18, 2001; 276(21): 18321 - 18326.
[Abstract] [Full Text] [PDF]

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