Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation and airway hyperresponsiveness in mice

R. Stokes Peebles, Koichi Hashimoto, Jason D. Morrow, Ryszard Dworski, Robert D. Collins, Yuko Hashimoto, John W. Christman, Kyung Ho Kang, Kasia Jarzecka, Jamye Furlong, Daphne B. Mitchell, Megha Talati, Barney S. Graham, James R. Sheller

Research output: Contribution to journalArticle

97 Citations (Scopus)

Abstract

Nonselective cyclooxygenase (COX) inhibition during allergic sensitization with ovalbumin in a murine model leads to an increase in the Type 2 cytokines interleukin-5 (IL-5) and IL-13; however, the effect of selective COX-1 and COX-2 inhibitors on these cytokines is unknown. We found that COX-1 protein was constitutively expressed in lung tissue. Expression of COX-1 protein did not increase with ovalbumin sensitization, but expression of COX-2 protein did. Ovalbumin-sensitized mice treated with either selective COX-1 inhibitor SC58560 (OVA-COX-1 inhibitor) or selective COX-2 inhibitor SC58236 (OVA-COX-2 inhibitor) had significantly greater airway hyperresponsiveness (p < 0.05) and higher levels of IL-13 (p < 0.05) in lung supernatants than did untreated mice that were ovalbumin sensitized (OVA). Lung mRNA levels for the chemokine receptors CCR1 through CCR5 (expressed on eosinophils, basophils, lymphocytes, and dendritic cells) were increased in the OVA-COX-2 inhibitor and OVA-indomethacin groups. We conclude that in the BALB/c mouse, COX inhibition with either a COX-1 or COX-2 inhibitor during allergen sensitization augments production of IL-13 and increases airway hyperresponsiveness.

Original languageEnglish
Pages (from-to)1154-1160
Number of pages7
JournalAmerican Journal of Respiratory and Critical Care Medicine
Volume165
Issue number8
DOIs
Publication statusPublished - 2002 Apr 15
Externally publishedYes

Keywords

  • Airway hyperresponsiveness
  • Cyclooxygenase
  • IL-13
  • Ovalbumin

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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  • Cite this

    Stokes Peebles, R., Hashimoto, K., Morrow, J. D., Dworski, R., Collins, R. D., Hashimoto, Y., Christman, J. W., Kang, K. H., Jarzecka, K., Furlong, J., Mitchell, D. B., Talati, M., Graham, B. S., & Sheller, J. R. (2002). Selective cyclooxygenase-1 and -2 inhibitors each increase allergic inflammation and airway hyperresponsiveness in mice. American Journal of Respiratory and Critical Care Medicine, 165(8), 1154-1160. https://doi.org/10.1164/ajrccm.165.8.2106025