| Asthma is a common chronic inflammatory disease in respiratory system resulted from genetic and environmental factors, including regulation of a variety of proinflammatory mediators. The essence of asthma is chronic airway inflammation. The airway inflammation exist all the time in spite of the courses of disease may occur as acute phase or chronic phase. The elimination or control of airway inflammation is the key to cure asthma. Therefore, it's necessary to investigate the mechanisms involve in the genesis and development of airway inflammation.NF-κB plays critical role in transcription regulation of many immune and inflammatory reaction genes, p50 and c-Rel subunit of NF-κB are identified as the key molecules of asthmatic airway inflammation. CARM1 is a transcriptional coactivator which NF-κB dependent on and acts as a promoter-specific regulator of NF-κB recruitment to chromatin. CARM1 may be activate NF-κB signal transduction pathway by enhancing NF-κB recruitment to cognate sites and initate transcription of a variety of proinflammatory and immunoregulation genes,which plays critical role in transcription regulation of immune and inflammatory reaction genes. Gene subset which NF-κB dependening on needs CARM1 induction and CARM1 is a necessary NF-κB coactivator. CARM1 catalyze methylation of Arg 2, Arg 17 and Arg 26 of histone H3,Arginine methylation involve in manifold cellular processes like signaling, transcription regulation, chromatin remolding ,and apoptosis with Extensive biology function. The mechanism of CARM1 and NF-κB in asthma are unclear now. The experiment investigated the expression of CARM1 and NF-κB(P65)and the interference effect of dexamethasone in asthma by preparation OVA guinea pigs asthma mode. We try to illuminate the potential mechanisms of CARM1and NF-κB in asthma from proinflammatory mediator transcription regulation.Methods Forty white male guinea pigs were randomly Divided into three groups: control group, asthma group and dexamethasone administration group. Asthma model was established by OVA-sensitization and OVA-challenge; normal saline with the same dosage replace OVA in control group ; dexamethasone intraperitoneal inject after each antigen challenge in dexamethasone administration group and other processes the same as model group. Perfusion-fixed tissue that made 24 hours after the last challenge were made into frozen section and pathological change were Observed under light microscope after HE stain. Indirect immunofluorescence were used to detect CARM1 and NF-κB(P65)expression in airway and lungs . Ten high-power fields were counted randomly each specimen and average positive cell numbers were calculated. Data of each groups ware expressed as mean+/-standard deviation and mean multiple comparison between all groups use Dunnett T3 test.Results The positive expression of CARM1and NF-κB(P65)were detected in all groups, they are mainly expressed in airway and lungs. The expression of CARM1 and NF-κB(P65)significantly increased in asthma group[(123.75±41.55)and(126.92±46.74)/400 field]and dexamethasone group [(84.33±27.70)and(85.00±29.22)/400 field] compare with the control group[(51.67±8.29)and(52.75±9.07)/400 field].The expression of dexamethasone group decreased compare with the asthma group and multiple comparison has statistical significance between all groups.Conclusion CARM1 and NF-κB(P65) highly express in airway and lungs of asthmatic guinea pigs. These results suggest that CARM1 may be activate NF-κB signal transduction pathway by enhancing NF-κB recruitment to cognate sites and initating transcriptional activation of a variety of proinflammatory and immunoregulation gene, and then resulting asthma inflammatory reaction. CARM1 and NF-κB(P65)are involve in transcriptional regulation of proinflammatory mediators and it is one of the important molecule mechanism in the genesis and development of asthma. Dexamethasone downregulate the expression of CARM1and NF-κB in the airway and lungs and alleviate asthma inflammatory reaction by partial blocking proinflanmmatory mediators. The accurate mechanism is need to develop further investigation.
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