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Review
, 20 (2), 87-103

Tumor Necrosis Factor-α Signaling in Macrophages

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Review

Tumor Necrosis Factor-α Signaling in Macrophages

Narayanan Parameswaran et al. Crit Rev Eukaryot Gene Expr.

Abstract

Tumor necrosis factor-α (TNFα) was cloned over 2 decades ago and its identification in part led to the discovery of a super family of tumor necrosis factors (TNFs) and their receptors. TNFα signals through two transmembrane receptors, TNFR1 and TNFR2, and regulates a number of critical cell functions including cell proliferation, survival, differentiation, and apoptosis. Macrophages are the major producers of TNFα and interestingly are also highly responsive to TNFα. Aberrant TNFα production and TNF receptor signaling have been associated with the pathogenesis of several diseases, including rheumatoid arthritis, Crohn's disease, atherosclerosis, psoriasis, sepsis, diabetes, and obesity. TNFα has been shown to play a pivotal role in orchestrating the cytokine cascade in many inflammatory diseases and because of this role as a "master-regulator" of inflammatory cytokine production, it has been proposed as a therapeutic target for a number of diseases. Indeed anti-TNFα drugs are now licensed for treating certain inflammatory diseases including rheumatoid arthritis and inflammatory bowel disease. In this review we discuss the discovery of TNFα and its actions especially in regulating macrophage biology. Given its importance in several human diseases, we also briefly discuss the role of anti-TNFα therapeutics in the treatment of inflammatory diseases.

Figures

FIGURE 1
FIGURE 1
Signaling from TNFα receptors.
FIGURE 2
FIGURE 2
TNFα plays a central role in the perpetuation of inflammation in chronic diseases.
FIGURE 3
FIGURE 3
TNFα and its receptors play a major role in a number of inflammatory diseases. Anti-TNFα agents are clinically used to treat some of these diseases.

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