Tumor necrosis factor alpha, citrullination, and peptidylarginine deiminase 4 in lung and joint inflammation.

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Arthritis research & therapy, ISSN: 1478-6362, Vol: 18, Issue: 1, Page: 173

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Bawadekar, Mandar; Gendron-Fitzpatrick, Annette; Rebernick, Ryan; Shim, Daeun; Warner, Thomas F.; Nicholas, Anthony P.; Lundblad, Lennart K., A; Thompson, Paul R.; Shelef, Miriam A.
Springer Nature
Medicine; Immunology and Microbiology; Citrullination; Experimental arthritis; Lung; Peptidylarginine deiminase 4; Rheumatoid arthritis; TNF-α; Biochemistry; Enzymes and Coenzymes; Musculoskeletal Diseases; Rheumatology
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The relationship between lung and joint inflammation in rheumatoid arthritis is poorly understood. Lung inflammation with resultant protein citrullination may trigger anti-citrullinated protein antibodies, inflammation, and arthritis. Alternatively, lung and joint inflammation may be two manifestations of a single underlying pathology. The lung has increased citrullination and TNF-α levels are high in rheumatoid arthritis; however, it is unknown if TNF-α can induce lung protein citrullination. The citrullinating enzyme peptidylarginine deiminase 4 (PAD4) exacerbates TNF-α-induced arthritis, but a role for PAD4 in lung citrullination and TNF-α-induced lung inflammation has not been explored. Our aim was to use TNF-α-overexpressing mice to clarify the intersection of TNF-α, citrullination, PAD4, arthritis, and lung inflammation.