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Review
. 2010;20(2):87-103.
doi: 10.1615/critreveukargeneexpr.v20.i2.10.

Tumor necrosis factor-α signaling in macrophages

Narayanan Parameswaran  1 , Sonika Patial
Affiliations
Review

Tumor necrosis factor-α signaling in macrophages

Narayanan Parameswaran et al. Crit Rev Eukaryot Gene Expr. 2010.

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.

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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.
See this image and copyright information in PMC

References

    1. O'Malley WE, Achinstein B, Shear MJ. Action of bacterial polysaccharide on tumors. II. Damage of sarcoma 37 by serum of mice treated with Serratia Marcescens polysaccharide, and induced tolerance. J Natl Cancer Inst. 1962;29:1169–1175. - PubMed
    1. Carswell EA, Old LJ, Kassel RL, Green S, Fiore N, Williamson B. An endotoxin-induced serum factor that causes necrosis of tumors. Proc Natl Acad Sci U S A. 1975 Sep;72(9):3666–3670. - PMC - PubMed
    1. Pennica D, Nedwin GE, Hayflick JS, Seeburg PH, Derynck R, Palladino MA, Kohr WJ, Aggarwal BB, Goeddel DV. Human tumour necrosis factor: precursor structure, expression and homology to lymphotoxin. Nature. 312(5996):724–729. 1984 Dec 20–1985 Jan 2. - PubMed
    1. Pennica D, Hayflick JS, Bringman TS, Palladino MA, Goeddel DV. Cloning and expression in Escherichia coli of the cDNA for murine tumor necrosis factor. Proc Natl Acad Sci U S A. 1985 Sep;82(18):6060–6064. - PMC - PubMed
    1. Aggarwal BB, Kohr WJ, Hass PE, Moffat B, Spencer SA, Henzel WJ, Bringman TS, Nedwin GE, Goeddel DV, Harkins RN. Human tumor necrosis factor. Production, purification, and characterization. J Biol Chem. 1985 Feb 25;260(4):2345–2354. - PubMed

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