Document Detail

In vivo modulation of the inflammatory response by non-steroidal anti-inflammatory drug-related compounds that TRIGGER L-selectin shedding.
MedLine Citation:
PMID:  22975861     Owner:  NLM     Status:  Publisher    
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.
Ada Herrera-García; María Domínguez-Luis; Mayte Arce-Franco; Judith López-Fernández; Manuel Feria; Olga Barreiro; Francisco Sánchez-Madrid; Federico Díaz-González
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-9-14
Journal Detail:
Title:  European journal of immunology     Volume:  -     ISSN:  1521-4141     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-9-14     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Servicio de Reumatología, Hospital Universitario de Canarias, La Laguna, Spain.
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