title: COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization.
abstract: BACKGROUND
  Mechanical injury to the skin by scratching is an important feature of atopic dermatitis (AD).
  
  
  OBJECTIVE
  To investigate the role of COX-2 in allergic skin inflammation elicited by epicutaneous (EC) sensitization via introduction of ovalbumin through shaved tape-stripped skin.
  
  
  METHODS
  COX-2 mRNA was measured by quantitative PCR, and COX-2 protein was measured by Western blotting. We investigated the effect of administration of the COX-2 selective inhibitor NS-398 during EC sensitization with ovalbumin in a mouse model of AD characterized by eosinophil skin infiltration, elevated total and antigen specific IgE, and a systemic TH2 response to antigen. We further examined the response of COX-2-deficient mice to EC immunization with ovalbumin.
  
  
  RESULTS
  Tape stripping caused a transient increase in skin COX-2 mRNA. In contrast, COX-2 mRNA was not increased after ovalbumin sensitization. Infiltration by eosinophils and expression of IL-4 mRNA in ovalbumin-sensitized skin sites, ovalbumin specific IgE and IgG1 antibody responses, and IL-4 secretion by splenocytes after ovalbumin stimulation were all significantly increased in EC mice that received NS-398. In contrast, ovalbumin specific IgG 2a antibody response and IFN-gamma secretion by splenocytes after ovalbumin stimulation were significantly decreased in these mice. COX-2-deficient mice also exhibited an enhanced systemic TH2 response to EC sensitization.
  
  
  CONCLUSIONS
  These results demonstrate that COX-2 limits the TH2 response to EC sensitization and suggest that COX inhibitors may worsen allergic skin inflammation in patients with AD.
authors.affiliation: Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
authors.forename: Dhafer
authors.initials: D
authors.lastname: Laouini
authors.forename: Abdala
authors.initials: A
authors.lastname: Elkhal
authors.forename: Ali
authors.initials: A
authors.lastname: Yalcindag
authors.forename: Seiji
authors.initials: S
authors.lastname: Kawamoto
authors.forename: Hans
authors.initials: H
authors.lastname: Oettgen
authors.forename: Raif S
authors.initials: RS
authors.lastname: Geha
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003876:Dermatitis, Atopic / Q000276:immunology; D007073:Immunoglobulin E / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D012867:Skin / Q000201:enzymology / Q000276:immunology*; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007074:Immunoglobulin G; D012333:RNA, Messenger; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases