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Regulation of Activin A Expression in Mast Cells and Asthma: Its Effect on the Proliferation of Human Airway Smooth Muscle Cells¹

Seong H. Cho^*, Zhengbin Yao, Shen-Wu Wang, Rodrigo F. Alban^*, Richard G. Barbers, Samuel W. French and Chad K. Oh^2,*

^* Division of Allergy and Immunology, Department of Pediatrics, and Department of Pathology, University of California, Los Angeles School of Medicine, Harbor-University of California, Los Angeles Medical Center, Torrance, CA 90509; Tanox, Inc., Houston, TX 77025; and Division of Pulmonary and Critical Care Medicine, University of Southern California School of Medicine, Los Angeles, CA 90033

Activin A, a homodimeric protein (AA) and a member of the TGF- superfamily, is involved in the inflammatory repair process. Using cDNA microarray analysis, we discovered strong induction of the activin A gene in human mast cells (MC) on stimulation with PMA and calcium ionophore (A23187). Activin A mRNA was also highly induced in primary cultured murine bone marrow MC (BMMC) after stimulation by IgE receptor cross-linking. Secretion of activin A was evident in human mast cell-1 line cells 3 h after stimulation and progressively increased over time. Activin A was present in the cytoplasm of activated but not unstimulated murine bone marrow MC as demonstrated by immunofluorescence studies, suggesting that secretion of activin A by MC was due to de novo synthesis rather than secretion of preformed protein. Activin A also colocalized with human lung MC from patients with asthma by double-immunofluorescence staining. Furthermore, secretion of activin A was significantly increased in the airway of wild-type mice after OVA sensitization followed by intranasal challenge. Secretion of activin A, however, was greatly reduced in MC-deficient WBB6F₁-W/W^v mice as compared with wild-type mice, indicating that MC are an important contributor of activin A in the airways of a murine asthma model. Additionally, activin A promoted the proliferation of human airway smooth muscle cells. Taken together, these data suggest that MC-derived activin A may play an important role in the process of airway remodeling by promoting the proliferation of airway smooth muscle.

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The JI 2003 170: 3937-3938. [Full Text]  

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