The Journal of Immunology, Vol 155, Issue 12 5826-5834, Copyright © 1995 by American Association of Immunologists

ARTICLES

Augmentation or inhibition of IFN-gamma-induced MHC class II expression by lipopolysaccharides. The roles of TNF-alpha and nitric oxide, and the importance of the sequence of signaling

SC Sicher, GW Chung, MA Vazquez and CY Lu
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235, USA.

MHC class II expression on macrophages is one determinant of Ag presentation and the vigor of CD4+ T cell immunity. We show that LPS may either inhibit or augment IFN-gamma-induced MHC class II on macrophages depending on the sequence of the IFN-gamma and LPS signals. LPS inhibited MHC class II when added simultaneously with IFN-gamma, but augmented class II expression when added after IFN-gamma. Inhibition was due to nitric oxide (NO), which was only produced if LPS was given simultaneously with IFN-gamma. However, even when NO production was inhibited, LPS given simultaneously with IFN-gamma did not augment MHC class II expression. This suggests that LPS delivers different signals when given simultaneously vs after IFN-gamma. LPS augmentation of class II expression was functionally important because it correlated with increased Ag presentation. Augmentation by LPS of IFN-gamma-induced class II expression by macrophages has not been previously reported. We found that TNF-alpha, like LPS, inhibited IFN- gamma-induced class II expression if NO was produced, but augmented it in the absence of NO formation. Studies with a neutralizing anti-TNF- alpha Ab, however, indicate that LPS augmentation of MHC class II did not require TNF-alpha. LPS augmentation involved a different mechanism than IFN-gamma induction of MHC class II. LPS augmentation occurred at a post-transcriptional level, whereas IFN-gamma-induction occurred at the level of gene transcription. LPS augmentation was apparent after 2 h of stimulation by LPS, while IFN-gamma induction of class II expression required more than 8 h.

This article has been cited by other articles:

				E. Z. Kincaid, A. J. Wolf, L. Desvignes, S. Mahapatra, D. C. Crick, P. J. Brennan, M. S. Pavelka Jr., and J. D. Ernst Codominance of TLR2-Dependent and TLR2-Independent Modulation of MHC Class II in Mycobacterium tuberculosis Infection In Vivo J. Immunol., September 1, 2007; 179(5): 3187 - 3195. [Abstract] [Full Text] [PDF]

				C. Casals, M. Barrachina, M. Serra, J. Lloberas, and A. Celada Lipopolysaccharide Up-Regulates MHC Class II Expression on Dendritic Cells through an AP-1 Enhancer without Affecting the Levels of CIITA J. Immunol., May 15, 2007; 178(10): 6307 - 6315. [Abstract] [Full Text] [PDF]

				Y. Yao, Q. Xu, M.-J. Kwon, R. Matta, Y. Liu, S.-C. Hong, and C.-H. Chang ERK and p38 MAPK Signaling Pathways Negatively Regulate CIITA Gene Expression in Dendritic Cells and Macrophages J. Immunol., July 1, 2006; 177(1): 70 - 76. [Abstract] [Full Text] [PDF]

				E. C. Tsark, W. Wang, Y.-C. Teng, D. Arkfeld, G. R. Dodge, and S. Kovats Differential MHC Class II-Mediated Presentation of Rheumatoid Arthritis Autoantigens by Human Dendritic Cells and Macrophages J. Immunol., December 1, 2002; 169(11): 6625 - 6633. [Abstract] [Full Text] [PDF]

				K. Wolk, W.-D. Docke, V. von Baehr, H.-D. Volk, and R. Sabat Impaired antigen presentation by human monocytes during endotoxin tolerance Blood, July 1, 2000; 96(1): 218 - 223. [Abstract] [Full Text] [PDF]

				F. Aloisi, R. De Simone, S. Columba-Cabezas, G. Penna, and L. Adorini Functional Maturation of Adult Mouse Resting Microglia into an APC Is Promoted by Granulocyte-Macrophage Colony-Stimulating Factor and Interaction with Th1 Cells J. Immunol., February 15, 2000; 164(4): 1705 - 1712. [Abstract] [Full Text] [PDF]

				Y. Han, Z-H. L. Zhou, and R. M. Ransohoff TNF-{alpha} Suppresses IFN-{gamma}-Induced MHC Class II Expression in HT1080 Cells by Destabilizing Class II trans-Activator mRNA J. Immunol., August 1, 1999; 163(3): 1435 - 1440. [Abstract] [Full Text] [PDF]

				S. Mukhopadhyay, P. K. Sahoo, A. George, V. Bal, S. Rath, and B. Ravindran Delayed Clearance of Filarial Infection and Enhanced Th1 Immunity Due to Modulation of Macrophage APC Functions in xid Mice J. Immunol., July 15, 1999; 163(2): 875 - 883. [Abstract] [Full Text] [PDF]

				E. Gonalons, M. Barrachina, J. A. Garcia-Sanz, and A. Celada Translational Control of MHC Class II I-A Molecules by IFN-{gamma} J. Immunol., August 15, 1998; 161(4): 1837 - 1843. [Abstract] [Full Text] [PDF]

				J. W. Lee, C. Beckham, B. R. Michel, H. Rosen, and H. J. Deeg HLA-DR-Mediated Signals for Hematopoiesis and Induction of Apoptosis Involve But Are Not Limited to a Nitric Oxide Pathway Blood, July 1, 1997; 90(1): 217 - 225. [Abstract] [Full Text] [PDF]