IL-4-DEPENDENT REGULATION OF TGF-ALPHA AND TGF-BETA-1 EXPRESSION IN HUMAN EOSINOPHILS

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 i nfiltrating hamster cutaneous wounds were found to express TGFs sequen tially. In this study, we examined the biologic mediators that may reg ulate the expression of TGF-alpha and -beta 1 by eosinophils. Eosinoph ils were isolated from the peripheral blood of healthy donors and cult ured in the absence or presence of IL-3, IL-4, and IL-5. Cells were an alyzed 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-reg ulated TGF-beta 1 mRNA and product expression by eosinophils in all do nors. Interestingly, TGF-alpha production by eosinophils was upregulat ed by IL-3 and IL-5 but was down-regulated by IL-4. Consistent with th e ability of IL-4 to regulate eosinophil responses, IL-4 signaling mol ecules are present in human eosinophils. The observation that IL-4 can differentially regulate the expression of TGF-alpha and TGF-beta 1 Su ggests that IL-4 may serve as a physiologic molecular switch of TGF ex pression by the infiltrating eosinophils in wound healing and carcinog enesis.