IL-4-dependent regulation of TGF-alpha and TGF-beta1 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-beta1. 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 -beta1 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-beta1 using TGF-specific ELISAs. IL-3, IL-4, and IL-5 independently up-regulated TGF-beta1 mRNA and product expression by eosinophils in all donors. Interestingly, TGF-alpha 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-alpha and TGF-beta1 suggests that IL-4 may serve as a physiologic molecular switch of TGF expression by the infiltrating eosinophils in wound healing and carcinogenesis.
Elovic
A E
AE
Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, MA 02215, USA.
Ohyama
H
H
Sauty
A
A
McBride
J
J
Tsuji
T
T
Nagai
M
M
Weller
P F
PF
Wong
D T
DT
D000328:Adult; D000818:Animals; D006224:Cricetinae; D004804:Eosinophils / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D015847:Interleukin-4 / Q000494:pharmacology / Q000502:physiology*; D015848:Interleukin-5 / Q000494:pharmacology; D021382:Protein Sorting Signals / Q000378:metabolism; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D007377:Interleukin-3; D015848:Interleukin-5; D021382:Protein Sorting Signals; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; D015534:Trans-Activators; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D015847:Interleukin-4