COX-2 inhibition enhances the TH2 immune response to epicutaneous sensitization.
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.
Laouini
Dhafer
D
Division of Immunology, Children's Hospital, Boston, MA 02115, USA.
Elkhal
Abdala
A
Yalcindag
Ali
A
Kawamoto
Seiji
S
Oettgen
Hans
H
Geha
Raif S
RS
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
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