Regulation of Peripheral Inflammation by Spinal p38 MAP Kinase in Rats 英文参考文献.docVIP

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Regulation of Peripheral Inflammation by Spinal p38 MAP Kinase in Rats 英文参考文献.doc

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Regulation of Peripheral Inflammation by Spinal p38 MAP Kinase in Rats 英文参考文献

o PL SMEDICINE RegulationofPeripheralInflammation bySpinalp38MAPKinaseinRats David L.Boyle1,Toni L.Jones2,Deepa Hammaker1,Camille I.Svensson2,Sanna Rosengren1,Salvatore Albani1, Linda Sorkin2,Gary S.Firestein1* 1DivisionofRheumatology,Allergy,andImmunology,UniversityofCaliforniaSanDiegoSchoolofMedicine,LaJolla,California,UnitedStatesofAmerica,2Departmentof Anesthesiology,UniversityofCaliforniaSanDiegoSchoolofMedicine,LaJolla,California,UnitedStatesofAmerica Funding:Thisworkwassupported bygrantsfromtheArthritis Foundation(GSF)andtheNational InstituteofArthritisand Musculoskeletal,andSkinDiseases (RO1AR47825)(GSF).Thefunders hadnoroleinstudydesign,data collectionandanalysis,decisionto publish,orpreparationofthe manuscript. ABSTRACT Background Somaticafferentinputtothespinalcordfromaperipheralinflammatorysitecanmodulate the peripheral response. However, the intracellular signaling mechanisms in the spinal cord that regulate this linkage have not been defined. Previous studies suggest spinal cord p38 mitogen-activatedprotein(MAP)kinaseandcytokinesparticipateinnociceptivebehavior.We therefore determined whether these pathways also regulate peripheral inflammation in rat adjuvantarthritis,whichisamodelofrheumatoidarthritis. CompetingInterests:Theauthors havedeclaredthatnocompeting interestsexist. AcademicEditor:TomHuizinga, LeidenUniversityMedicalCentre, Netherlands MethodsandFindings Selective blockade of spinal cord p38 MAP kinase by administering the p38 inhibitor SB203580viaintrathecal(IT)cathetersinratswithadjuvantarthritismarkedlysuppressedpaw swelling, inhibited synovial inflammation, and decreased radiographic evidence of joint destruction.ThesamedoseofSB203580deliveredsystemicallyhadnoeffect,indicatingthat the effect was mediated by local concentrations in the neural compartment. Evaluation of articular gene expression by quantitative real-time PCR showed that spinal p38 inhibition markedlydecreasedsynovialinterleukin-1andà6andmatrixmetalloproteinase(MMP3)ge