Mutual inhibition by TGF-β and IL-4 in cultured human bronchial epithelial cells

Yuichi Adachi, Tadashi Mio, Keiichi Takigawa, Ilja Striz, Debra J. Romberger, Richard A. Robbins, John R. Spurzem, Peggy Heires, Stephen I. Rennard

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

-The airway epithelial cell may play a role as an effector cell, releasing various cytokines and extracellular matrix components in immune responses, inflammation, and wound repair processes, thus contributing to cytokine "networks." The cytokines transforming growth factor (TGF)-β and interleukin (IL)-4 are thought to have pivotal roles in airway diseases, with IL-4 having proinflammatory actions and TGF-β generally regarded to mediate repair and to attenuate immune responses. In asthma, where IL-4 and TGF-β are thought to contribute to the inflammatory process and repair, respectively, interactions between these cytokines are likely to be of importance. Therefore, we studied the potential interaction of both cytokines by measuring IL-8 and fibronectin release by cultured human bronchial epithelial cells (HBECs). IL-4 is capable of inducing IL-8 release from HBECs. This effect of IL-4 can be blocked by the concurrent presence of the cytokine TGF-β. In contrast, TGF-β had a modest inconsistent stimulatory effect on IL-8 release by itself and had no effect on the IL-8 release induced by tumor necrosis factor (TNF)-a. An antagonistic effect of IL-4 and TGF-β was also observed on HBEC fibronectin release. TGF-β stimulated fibronectin release, and IL-4 was able to inhibit this. This effect was not due to a redistribution of fibronectin but appeared to be due to a true reduction in synthesis. Consistent with this, IL-4 and TGF-β effects on IL-8 and fibronectin release were paralleled by changes in mRNA levels. The ability of TGF-β to block IL-4-induced IL-8 release is certainly not the only mechanism to inhibit IL-8 release because dexamethasone was capable of inhibiting both TNF-α- and IL-4-induced release of IL-8. These results indicate that TGF-β and IL-4 can have mutually inhibitory effects. The balance determined by this reciprocal inhibition may play an important role in regulating inflammation repair and in diseases such as asthma.

Original languageEnglish (US)
Pages (from-to)L648-L655
JournalAmerican Journal of Physiology
Volume273
Issue number3 PART 1
StatePublished - 1997

Keywords

  • Fibronectin
  • Interleukin-4
  • Interleukin-8
  • Transforming growth factor-β

ASJC Scopus subject areas

  • Physiology (medical)

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