QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: jpet.106.104729v1 318/3/1315    most recent Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map 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 Bani-Hani, M. G. Articles by Motterlini, R. Search for Related Content PubMed PubMed Citation Articles by Bani-Hani, M. G. Articles by Motterlini, R.

INFLAMMATION, IMMUNOPHARMACOLOGY, AND ASTHMA

Modulation of Thrombin-Induced Neuroinflammation in BV-2 Microglia by Carbon Monoxide-Releasing Molecule 3

Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, United Kingdom (M.G.B.-H., C.J.G., R.M.); Department of Vascular Surgery, North West London Hospitals National Health Service Trust, Northwick Park Hospital, Harrow, United Kingdom (M.G.B.-H., D.G.); and Department of Chemistry, University of Sheffield, Sheffield, United Kingdom (B.E.M.)

Carbon monoxide-releasing molecules are emerging as a new class of pharmacological agents that regulate important cellular function by liberating CO in biological systems. Here, we examined the role of carbon monoxide-releasing molecule 3 (CORM-3) in modulating neuroinflammatory responses in BV-2 microglial cells, considering its practical application as a novel therapeutic alternative in the treatment of stroke. BV-2 microglia cells were incubated for 24 h in normoxic conditions with thrombin alone or in combination with interferon- to simulate the inflammatory response. Cells were also subjected to 12 h of hypoxia and reoxygenated for 24 h in the presence of thrombin and interferon-. In both set of experiments, the anti-inflammatory action of CORM-3 was evaluated by assessing its effect on nitric oxide production (nitrite levels) and tumor necrosis factor (TNF)- release. CORM-3 (75 µM) did not show any cytotoxicity and markedly attenuated the inflammatory response to thrombin and interferon- in normoxia and to a lesser extent in hypoxia as evidenced by a reduction in nitrite levels and TNF- production. Inactive CORM-3, which does not liberate CO and is used as a negative control, failed to prevent the increase in inflammatory mediators. Blockade of endogenous CO production by tin protoporphyrin-IX did not change the anti-inflammatory activity of CORM-3, suggesting that CO liberated from the compound is responsible for the observed effects. In addition, inhibition of the mitogen-activated protein kinases phosphatidyl inositol 3 kinase and extracellular signal-regulated kinase amplified the anti-inflammatory effect of CORM-3. These results suggest that the anti-inflammatory activity of CORM-3 could be exploited to mitigate microglia activity in stroke and other neuroinflammatory diseases.

Address correspondence to: Roberto Motterlini, Vascular Biology Unit, Department of Surgical Research, Northwick Park Institute for Medical Research, Harrow, Middlesex HA1 3UJ, United Kingdom. E-mail: r.motterlini{at}imperial.ac.uk

This article has been cited by other articles:

				M. I. Guillen, J. Megias, V. Clerigues, F. Gomar, and M. J. Alcaraz The CO-releasing molecule CORM-2 is a novel regulator of the inflammatory process in osteoarthritic chondrocytes Rheumatology, July 11, 2008; (2008) ken264v1. [Abstract] [Full Text] [PDF]

				J. Megias, M. I. Guillen, A. Bru, F. Gomar, and M. J. Alcaraz The Carbon Monoxide-Releasing Molecule Tricarbonyldichlororuthenium(II) Dimer Protects Human Osteoarthritic Chondrocytes and Cartilage from the Catabolic Actions of Interleukin-1{beta} J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 56 - 61. [Abstract] [Full Text] [PDF]