ABSTRACT
Cogan's syndrome is a rare chronic inflammatory disease of unknown origin, characterized by nonsyphilitic interstitial keratitis, vestibuloauditory dysfunction and vasculitis. Cogan's syndrome is uncommon and few cases have been published. A case of Cogan's syndrome in a patient with anti-Ro and anti-La positivity is described. A 24-year-old woman visited to department of rheumatology with dry mouth, dry eye, and vertigo on August 2004, and interstitial keratitis had developed on October 2004. She was admitted to the otolaryngology department with rapidly progressive hearing loss on December 2004. The patient's audiogram revealed severe sensorineural deafness. The patient was treated with systemic corticosteroid and methotrexate. This case is the first to report a case of Cogan's syndrome associated with anti-Ro and anti-La positivity.
Subject(s)
Female , Humans , Young Adult , Antibodies , Cogan Syndrome , Deafness , Hearing Loss , Keratitis , Methotrexate , Mouth , Otolaryngology , Rheumatology , Vasculitis , VertigoABSTRACT
15-deoxy-delta12,14-PGJ2(15d-PGJ2) is a natural ligand that activates the peroxisome proliferators-activated receptor (PPAR) gamma, a member of nuclear receptor family implicated in regulation of lipid metabolism and adipocyte differentiation. Recent studies have shown that 15d-PGJ2 is the potent anti-inflammatory agent functioning via PPARgamma-dependent and -independent mechanisms. Most postulated mechanisms for anti-inflammatory action of PPARgamma agonists are involved in inhibiting NF-kappaB signaling pathway. We examined the possibility that IL-6 signaling via the Jak-Stat pathway is modulated by 15d-PGJ2 in lymphocytes and also examined whether the inhibition of IL-6 signaling is dependent of PPARgamma. 15d-PGJ2 blocked IL-6 induced Stat1 and Stat3 activation in primary human lymphocytes, Jurkat cells and immortalized rheumatoid arthritis B cells. Inhibition of IL-6 signaling was induced rapidly within 15 min after treatment of 15d-PGJ2. Other PPARgamma-agonists, such as troglitazone and ciglitazone, did not inhibit IL-6 signaling, indicating that 15d-PGJ2 affect the IL-6-induced Jak-Stat signaling pathway via PPARgamma-independent mechanism. Although cycloheximide reversed 15d-PGJ2-mediated inhibition of Stat3 activation, actinomycin D had no effect on 15d-PGJ2-mediated inhibition of IL-6 signaling, indicating that inhibition of IL-6 signaling occur independent of de novo gene expression. These results show that 15d-PGJ2 specifically inhibit Jak-Stat signaling pathway in lymphocytes, and suggest that 15d-PGJ2 may regulate inflammatory reactions through the modulation of different signaling pathway other than NF-kappaB in lymphocytes.