[Frontiers in Bioscience 14, 2765-2778, January 1, 2009]

Mechanism of cytokine modulation of epithelial tight junction barrier

Rana Al-Sadi1, Michel Boivin2, Thomas Ma2

1Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131, 2Department of Internal Medicine, University of New Mexico School of Medicine, Albuquerque, NM 87131


1. Abstract
2. Introduction
3. Cytokine modulation of intestinal epithelial tight junction barrier
3.1. Interferon Gamma (IFN-γ)
3.2. Tumor Necrosis Factor-alpha (TNF-alpha)
3.3. Interleukin-1 beta (IL-1beta)
3.4. Interleukin-2 (IL-2)
3.5. Interleukin-4 (IL-4)
3.6. Interleukin-6 (IL-6)
3.7. Interleukin-10 (IL-10)
3.8. Interleukin-11 (IL-11)
3.9. Interleukin-13 (IL-13)
3.10. Interleukin 15 (IL-15)
3.11. Interleukin 15 (IL-17)
3.12. Other Interleukins
3.13. Interferon alpha and beta (IFN-α and IFN-β)
3.14. Transforming Growth Factor alpha (TGF-α)
3.15. Transforming Growth Factor beta (TGF-β)
4. Summary and perspective
5. Acknowledgments
6. References


Cytokines play a crucial role in the modulation of inflammatory response in the gastrointestinal tract. Pro-inflammatory cytokines including tumor necrosis factor-alpha, interferon-gamma, interleukin-1betaIL-1beta, and interleukin-12 are essential in mediating the inflammatory response, while anti-inflammatory cytokines including interleukin-10 and transforming growth factor-beta are important in the attenuation or containment of inflammatory process. It is increasingly recognized that cytokines have an important physiological and pathological effect on intestinal tight junction (TJ) barrier. Consistent with their known pro-inflammatory activities, pro-inflammatory cytokines cause a disturbance in intestinal TJ barrier, allowing increased tissue penetration of luminal antigens. Recent studies indicate that the inhibition of cytokine induced increase in intestinal TJ permeability has an important protective effect against intestinal mucosal damage and development of intestinal inflammation. In this review, the effects of various pro-inflammatory and anti-inflammatory cytokines on intestinal TJ barrier and the progress into the mechanisms that mediate the cytokine modulation of intestinal TJ barrier are reviewed.