Porphyrins as new endogenous anti-inflammatory agents

• Published in: European journal of pharmacology Vol. 691; no. 1-3; pp. 251 - 260
• Main Authors: Jelić, Dubravko, Tatić, Iva, Trzun, Marija, Hrvačić, Boška, Brajša, Karmen, Verbanac, Donatella, Tomašković, Marija, Čulić, Ognjen, Antolović, Roberto, Glojnarić, Ines, Weygand-Đurašević, Ivana, Vladimir-Knežević, Sanda, Mildner, Boris
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.09.2012
• Subjects: Animals; anti-inflammatory agents; Anti-Inflammatory Agents - metabolism; Anti-Inflammatory Agents - pharmacology; carcinogenesis; Cell Line, Tumor; Cell Proliferation - drug effects; Computational Biology; Cytokine; diabetes; free radicals; Fyn; Humans; in vitro studies; Inflammation; inflammatory bowel disease; Kinetics; Lipopolysaccharides - pharmacology; Lymphocytes - cytology; Lymphocytes - drug effects; Male; Mice; Molecular Docking Simulation; Porphyrins; Porphyrins - metabolism; Porphyrins - pharmacology; Protein Kinase Inhibitors - metabolism; Protein Kinase Inhibitors - pharmacology; Protein Structure, Tertiary; Proto-Oncogene Proteins c-fyn - antagonists & inhibitors; Proto-Oncogene Proteins c-fyn - chemistry; Proto-Oncogene Proteins c-fyn - metabolism; Respiratory Burst - drug effects; rheumatoid arthritis; Sf9 Cells; signal transduction; Spodoptera; T-lymphocyte; Thymidine - metabolism; TNF-α; tumor necrosis factor-alpha; Tumor Necrosis Factor-alpha - biosynthesis; tyrosine; T-lymphocyte; Fyn; Inflammation; TNF-α; Cytokine; Porphyrins
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2012.05.049

A series of porphyrins, tetrapyrrole natural organic compounds, are evaluated here as endogenous anti-inflammatory agents. They directly inhibit the activity of Fyn, a non-receptor Src-family tyrosine kinase, triggering anti-inflammatory events associated with down-regulation of T-cell receptor signal transduction, leading to inhibition of tumor necrosis factor alpha (TNF-α) production. This is one of the major pro-inflammatory cytokines, associated with diseases such as diabetes, tumorigenesis, rheumatoid arthritis, and inflammatory bowel disease. Porphyrins, as a chemical class, inhibited Fyn kinase activity in a non-competitive, linear-mixed fashion. In cell-based in vitro experiments on polymorphonuclear cells, porphyrins inhibited TNF-α cytokine production, T-cell proliferation, and the generation of free radicals in the oxidative burst, in a concentration-related manner. In vivo, lipopolysaccharide-induced TNF-α production in mice was inhibited by several of the porphyrins. These findings may be very important for the overall understanding of the role(s) of porphyrins in inflammation and their possible application as new anti-inflammatory agents. [Display omitted]