Calpain inhibitor I reduces the development of acute and chronic inflammation

S. Cuzzocrea, M. C. McDonald, E. Mazzon, D. Siriwardena, I. Serraino, L. Dugo, D. Britti, G. Mazzullo, A. P. Caputi, C. Thiemermann

Research output: Contribution to journalArticle

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Abstract

There is limited evidence that inhibition of the activity of the protease calpain I reduces inflammation. Here we investigate the effects of calpain inhibitor I in animal models of acute and chronic inflammation (carrageenan-induced pleurisy and collagen-induced arthritis). We report here for the first time that calpain inhibitor I (given at 5, 10, or 20 mg/kg i.p. in the pleurisy model or at 5 mg/kg i.p every 48 hours in the arthritis model) exerts potent anti-inflammatory effects (eg, inhibition of pleural exudate formation, mononuclear cell infiltration, delayed the development of the clinical signs and histological injury) in vivo. Furthermore, calpain inhibitor I reduced (1) the staining for nitrotyrosine and poly (ADP-ribose) polymerase (immunohistochemistry) and (2) the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lungs of carrageenan-treated rats and in joints from collagen-treated rats. Thus, prevention of the activation of calpain I reduces the development of acute and chronic inflammation. Inhibition of calpain I activity may represent a novel therapeutic approach for the therapy of inflammation.

Original languageEnglish
Pages (from-to)2065-2079
Number of pages15
JournalAmerican Journal of Pathology
Volume157
Issue number6
Publication statusPublished - 2000

Fingerprint

Calpain
Inflammation
Pleurisy
Carrageenan
Experimental Arthritis
Poly(ADP-ribose) Polymerases
Nitric Oxide Synthase Type II
Exudates and Transudates
Cyclooxygenase 2
Arthritis
Peptide Hydrolases
Anti-Inflammatory Agents
Collagen
Animal Models
Joints
Immunohistochemistry
Staining and Labeling
Lung
calpain inhibitors
Wounds and Injuries

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Cuzzocrea, S., McDonald, M. C., Mazzon, E., Siriwardena, D., Serraino, I., Dugo, L., ... Thiemermann, C. (2000). Calpain inhibitor I reduces the development of acute and chronic inflammation. American Journal of Pathology, 157(6), 2065-2079.

Calpain inhibitor I reduces the development of acute and chronic inflammation. / Cuzzocrea, S.; McDonald, M. C.; Mazzon, E.; Siriwardena, D.; Serraino, I.; Dugo, L.; Britti, D.; Mazzullo, G.; Caputi, A. P.; Thiemermann, C.

In: American Journal of Pathology, Vol. 157, No. 6, 2000, p. 2065-2079.

Research output: Contribution to journalArticle

Cuzzocrea, S, McDonald, MC, Mazzon, E, Siriwardena, D, Serraino, I, Dugo, L, Britti, D, Mazzullo, G, Caputi, AP & Thiemermann, C 2000, 'Calpain inhibitor I reduces the development of acute and chronic inflammation', American Journal of Pathology, vol. 157, no. 6, pp. 2065-2079.
Cuzzocrea S, McDonald MC, Mazzon E, Siriwardena D, Serraino I, Dugo L et al. Calpain inhibitor I reduces the development of acute and chronic inflammation. American Journal of Pathology. 2000;157(6):2065-2079.
Cuzzocrea, S. ; McDonald, M. C. ; Mazzon, E. ; Siriwardena, D. ; Serraino, I. ; Dugo, L. ; Britti, D. ; Mazzullo, G. ; Caputi, A. P. ; Thiemermann, C. / Calpain inhibitor I reduces the development of acute and chronic inflammation. In: American Journal of Pathology. 2000 ; Vol. 157, No. 6. pp. 2065-2079.
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