| In vivo modulation of the inflammatory response by non-steroidal anti-inflammatory drug-related compounds that TRIGGER L-selectin shedding. | |
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MedLine Citation:
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PMID: 22975861 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Diphenylamine-based non-steroidal anti-inflammatory drugs (NSAIDs) are able to cause in vitro the shedding of L-selectin. The aim of this work was to determine the physiologic relevance of L-selectin shedding in the anti-inflammatory effect exerted by NSAIDs in vivo. Chemical compounds structurally-related to NSAIDs - including diphenylamine, N-phenylanthranilic acid (N-Ph), diphenylacetic acid - as well as the traditional NSAID indomethacin were studied using the zymosan air-pouch mouse model. Animals intramuscularly pre-treated with indomethacin or N-Ph, but not with diphenylamine or diphenylacetic acid, showed a significant dose-dependent reduction in the number of neutrophils compared with untreated animals (N-Ph, IC50 = 6.7 mg/kg). Except for indomethacin, none of these compounds caused any significant reduction in cyclooxygenase-1 activity in vivo. In flow chamber experiments, N-Ph reduced the capability of human neutrophils to pass across the endothelial barrier by interfering with leukocyte rolling step on HUVEC. N-Ph, but not diphenylacetic acid, induced activation-independent L-selectin shedding in mouse neutrophils. Interestingly, N-Ph exerted an anti-inflammatory effect similar to that of the anti-L-selectin blocking antibody Mel-14, although no additive action was observed when both compounds were combined. These data suggest that the L-selectin shedding induced by NSAIDs may be involved in the anti-inflammatory action exerted by these compounds in clinical settings. |
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Authors:
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Ada Herrera-García; María Domínguez-Luis; Mayte Arce-Franco; Judith López-Fernández; Manuel Feria; Olga Barreiro; Francisco Sánchez-Madrid; Federico Díaz-González |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-9-14 |
Journal Detail:
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Title: European journal of immunology Volume: - ISSN: 1521-4141 ISO Abbreviation: Eur. J. Immunol. Publication Date: 2012 Sep |
Date Detail:
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Created Date: 2012-9-14 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 1273201 Medline TA: Eur J Immunol Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Servicio de Reumatología, Hospital Universitario de Canarias, La Laguna, Spain. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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