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and TGF-ß1 Expression in Human Eosinophils1
*
Division of Oral Pathology, Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, and
Department of Medicine, Harvard Medical School, Boston MA 02215; and
Department of Biochemistry, Iwate Medical University School of Dentistry, Iwate, Japan
TGFs play important roles in wound healing and carcinogenesis. We
have previously demonstrated that eosinophils infiltrating into
different pathologic processes elaborate TGF-
and TGF-ß1.
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- and -ß1 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- and
TGF-ß1 using TGF-specific ELISAs. IL-3, IL-4, and IL-5 independently
up-regulated TGF-ß1 mRNA and product expression by eosinophils in all
donors. Interestingly, TGF- production by eosinophils was
up-regulated 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- and TGF-ß1 suggests that IL-4 may serve as a physiologic
molecular switch of TGF expression by the infiltrating eosinophils in
wound healing and carcinogenesis.
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