This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Cuzzocrea, S. Articles by Thiemermann, C. Search for Related Content PubMed PubMed Citation Articles by Cuzzocrea, S. Articles by Thiemermann, C.

(American Journal of Pathology. 2000;157:145-158.)
© 2000 American Society for Investigative Pathology

Regular Articles

The Tyrosine Kinase Inhibitor Tyrphostin AG126 Reduces the Development of Acute and Chronic Inflammation

Salvatore Cuzzocrea^*, Michelle C. McDonald, Emanuela Mazzon, Dilani Siriwardena, Giusi Calabrò^*, Domenico Britti^§, Giuseppe Mazzullo^¶, Angela De Sarro^*, Achille P. Caputi^* and Christoph Thiemermann

From the Institute of Pharmacology,^*
University of Messina, Messina, Italy; the William Harvey Research Institute,
St. Bartholomew’s and The Royal London School of Medicine and Dentistry, London, United Kingdom; and the Department of Biomorphology,
the School of Medicine, the Department of Veterinary Medicine and Pharmacology,^§
and the Institute of Veterinary General Pathology and Pathological Anatomy,^¶
University of Messina, Messina, Italy

Protein tyrosine kinases help to regulate the expression of many genes that play important roles in inflammation. Here we investigate the effects of the tyrosine kinase inhibitor tyrphostin AG126 in two animal models of acute and chronic inflammation, carrageenan-induced pleurisy and collagen-induced arthritis. We report here that tyrphostin AG126 (given at 1, 3, or 10 mg/kg i.p. in the pleurisy model or 5 mg/kg i.p. every 48 hours in the arthritis model) exerts potent anti-inflammatory effects in animal models of acute and chronic inflammation in vivo. These include the inhibition of pleural exudate formation and mononuclear cell infiltration (pleurisy model) and the development of clinical signs and tissue injury (arthritis model). Furthermore, tyrphostin AG126 reduced the staining for nitrotyrosine and poly (ADP-ribose) polymerase (by immunohistochemistry) and the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated rats and in the joints from collagen-treated rats. Thus, we provide the first evidence that prevention of the activation of protein tyrosine kinases reduces the development of acute and chronic inflammation, and that inhibition of the activity of certain tyrosine kinases may represent a novel approach for the therapy of inflammation.

This article has been cited by other articles:

				J. M. Kahlenberg and G. R. Dubyak Mechanisms of caspase-1 activation by P2X7 receptor-mediated K+ release Am J Physiol Cell Physiol, May 1, 2004; 286(5): C1100 - C1108. [Abstract] [Full Text] [PDF]

				B. A. Moore, A. Turler, M. A. Pezzone, K. Dyer, J. Grandis, and A. J. Bauer Tyrphostin AG 126 inhibits development of postoperative ileus induced by surgical manipulation of murine colon Am J Physiol Gastrointest Liver Physiol, February 1, 2004; 286(2): G214 - G224. [Abstract] [Full Text] [PDF]

				S. Cuzzocrea, N. S. Wayman, E. Mazzon, L. Dugo, R. Di Paola, I. Serraino, D. Britti, P. K. Chatterjee, A. P. Caputi, and C. Thiemermann The Cyclopentenone Prostaglandin 15-Deoxy-Delta 12,14-Prostaglandin J2 Attenuates the Development of Acute and Chronic Inflammation Mol. Pharmacol., May 1, 2002; 61(5): 997 - 1007. [Abstract] [Full Text] [PDF]