IL-4-Dependent Regulation of TGF- alpha and TGF- beta 1 Expression in Human Eosinophils

• Published in: The Journal of immunology (1950) 1998-06, Vol.160 (12), p.6121-6127
• Main Authors: Elovic, A E, Ohyama, H, Sauty, A, McBride, J, Tsuji, T, Nagai, M, Weller, P F, Wong, DTW
• Format: Article
• Language: English
• ISSN: 0022-1767

TGFs play important roles in wound healing and carcinogenesis. We have previously demonstrated that eosinophils infiltrating into different pathologic processes elaborate TGF- alpha and TGF- beta 1. Eosinophils infiltrating hamster cutaneous wounds were found to express TGFs sequentially. In this study, we examined the biologic mediators that may regulate the expression of TGF- alpha and - beta 1 by eosinophils. Eosinophils were isolated from the peripheral blood of healthy donors and cultured in the absence or presence of IL-3, IL-4, and IL-5. Cells were analyzed by in situ hybridization and immunohistochemistry. Supernatants from these cultures were assayed for secreted TGF- alpha and TGF- beta 1 using TGF-specific ELISAs. IL-3, IL-4, and IL-5 independently up-regulated TGF- beta 1 mRNA and product expression by eosinophils in all donors. Interestingly, TGF- alpha production by eosinophils was upregulated by IL-3 and IL-5 but was down-regulated by IL-4. Consistent with the ability of IL-4 to regulate eosinophil responses, IL-4 signaling molecules are present in human eosinophils. The observation that IL-4 can differentially regulate the expression of TGF- alpha and TGF- beta 1 suggests that IL-4 may serve as a physiologic molecular switch of TGF expression by the infiltrating eosinophils in wound healing and carcinogenesis.