Expression of STAT6 and NF-κB p65 in the
colon mucosa of patients with ulcerative colitis
Expression of STAT6 and NF-κB p65 in the
colon mucosa of patients with ulcerative colitis
Rui ZHU MD,Heng FAN MD,Lin SHEN MD,Jianguo LIU BD,Jia ZHAO MM,
Department of Traditional
Chinese Medicine, Union Hospital, Tongji Medical College, Huazhong
University of Science and Technology, Wuhan 430022, China;
Abstract:The expression of signal transducer and activator of transcription 6 (STAT6) and nuclear factor-κB (NF-κB) in the colonic mucosa of patients with ulcerative colitis (UC) was examined. Real-time polymerase chain reaction and immunohistochemistry were used to detect the expression of STAT6 and NF-κB p65 at both mRNA and protein levels in the colonic mucosa of patients with UC and healthy volunteers. The results showed that the expression levels of STAT6 and NFκB p65 in the colonic mucosa of patients with UC were significantly higher than in normal controls at both mRNA and protein levels. These data suggest that STAT6 and NFκB p65 perhaps play an important role in the pathogenesis of UC and underscore the potential value of anti-UC strategies in the clinical management of this disease.
. Expression of STAT6 and NF-κB p65 in the
colon mucosa of patients with ulcerative colitis[J]. Front. Med., 2009, 3(4): 475-479.
Rui ZHU MD, Heng FAN MD, Lin SHEN MD, Jianguo LIU BD, Jia ZHAO MM, . Expression of STAT6 and NF-κB p65 in the
colon mucosa of patients with ulcerative colitis. Front. Med., 2009, 3(4): 475-479.
Lampinen M, Backman M, Winqvist O, Rorsman F, Rönnblom A, Sangfelt P, Carlson M. Differentregulation of eosinophil activity in Crohn’s disease comparedwith ulcerative colitis. J Leukoc Biol, 2008, 84(6): 1392―1399 doi: 10.1189/jlb.0807513
Lakatos L, Lakatos P L. Is the incidence and prevalenceof inflammatory bowel diseases increasing in Eastern Europe? Postgrad Med J, 2006, 82(967): 332―337 doi: 10.1136/pgmj.2005.042416
Shteingart S, Rapoport M, Grodzovski I, Sabag O, Lichtenstein M, Eavri R, Lorberboum-Galski H. Therapeuticpotency of IL2―caspase 3 targeted treatment in a murine experimentalmodel of inflammatory bowel disease. Gut, 2009, 58(6): 790―798 doi: 10.1136/gut.2008.153981
Trinatafillidis J K, Nasioulas G, Kosmidis P A. Colorectal cancer and inflammatory bowel disease: Epidemiology,risk factors, mechanisms of carcinogenesis and prevention strategies. Anticancer Res, 2009, 29(7): 2727―2737
Knight P, Campbell B J, Rhodes J M. Host-bacteria interaction in inflammatory bowel disease. Br Med Bull, 2008, 88(1): 95―113 doi: 10.1093/bmb/ldn038
Han W, Joo M, Everhart M B, Christman J W, Yull F E, Blackwell T S. Myeloid cells control termination of lung inflammationthrough the NF-kappaB pathway. Am J PhysiolLung Cell Mol Physiol, 2009, 296(3): 320―327 doi: 10.1152/ajplung.90485.2008
Cheng D S, Han W, Chen S M, Sherrill T P, Chont M, Park G Y, Sheller J R, Polosukhin V V, Christman J W, Yull F E, Blackwell T S. Airway epithelium controlslung inflammation and injury through the NF-kappaB Pathway. J Immunol, 2007, 178(10): 6504―6513
Alcamo E, Mizgerd J P, Horwitz B H, Bronson R, Beg A A, Scott M, Doerschuk C M, Hynes R O, Baltimore D. Targeted mutation of TNF receptor I rescues the RelA-deficientmouse and reveals a critical role for NF-κB in leukocyte recruitment. J Immunol, 2001, 167(3): 1592―1600
Wright J G, Christman J W. The role of nuclear factorkappa B in the pathogenesis of pulmonary diseases: implications fortherapy. Am J Respir Med, 2003, 2(3): 211―219
Lee H S, Moon C, Lee H W, Park E M, Cho M S, Kang J L. Src tyrosine kinases mediate activations of NF-κb and integrinsignal during lipopolysaccharide-induced acute lung injury. J Immunol, 2007, 179(10): 7001―7011
Sen P, Wallet M A, Yi Z, Huang Y, Henderson M, Mathews C E, Earp H S, Matsushima G, Baldwin A S Jr, Tisch R M. Apoptoticcells induce Mer tyrosine kinase-dependent blockade of NF-kappaB activationin dendritic cells. Blood, 2007, 109(2): 653―660 doi: 10.1182/blood-2006-04-017368
Kato T Jr, Delhase M, Hoffmann A, Karin M. CK2 Is a C-TerminalIkappaB Kinase Responsible for NF-kappaB Activation during the UVResponse. Mol Cell, 2003, 12(4): 829―839 doi: 10.1016/S1097-2765(03)00358-7
Tergaonkar V, Bottero V, Ikawa M, Li Q, Verma I M. IkappaB kinase-independent IkappaBalphadegradation pathway: functional NF-kappaB activity and implicationsfor cancer therapy. Mol Cell Biol, 2003, 23(22): 8070―8083 doi: 10.1128/MCB.23.22.8070-8083.2003
Baldwin A S Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu Rev Immunol, 1996, 14: 649―683 doi: 10.1146/annurev.immunol.14.1.649
Jones M R, Simms B T, Lupa M M, Kogan M S, Mizgerd J P. Lung NF-kappaB activationand neutrophil recruitment require IL-1 and TNF receptor signalingduring pneumococcal pneumonia. J Immunol, 2005, 175(11): 7530―7535
Sweeney C, Li L, Shanmugam R, Bhat-Nakshatri P, Jayaprakasan V, Baldridge L A, Gardner T, Smith M, Nakshatri H, Cheng L. Nuclear factor-kappaBis constitutively activated in prostate cancer in vitro and is overexpressedin prostatic intraepithelial neoplasia and adenocarcinoma of the prostate. Clin Cancer Res, 2004, 10(16): 5501―5507 doi: 10.1158/1078-0432.CCR-0571-03
Karin M, Cao Y, Greten F R, Li Z W. NF-kappaB in cancer: from innocent bystander to major culprit. Nat Rev Cancer, 2002, 2(4): 301―310 doi: 10.1038/nrc780
Caamaño J, Hunter C A. NF-kappaB family of transcriptionfactors: central regulators of innate and adaptive immune functions. Clin Microbiol Rev, 2002, 15(3): 414―429 doi: 10.1128/CMR.15.3.414-429.2002
Li Q, Verma I M. NF-kappaB regulation in theimmune system. Nat Rev Immunol, 2002, 2(10): 725―734 doi: 10.1038/nri910
Senftleben U, Li Z W, Baud V, Karin M. IKKbeta isessential for protecting T cells from TNFalpha-induced apoptosis. Immunity, 2001, 14(3): 217―230 doi: 10.1016/S1074-7613(01)00104-2
Mora A, Youn J, Keegan A, Boothby M. NF-kappaB/Rel participation in the lymphokine-dependent proliferation of Tlymphoid cells. J Immunol, 2001, 166(4): 2218―2227
Hettmann T, DiDonato J, Karin M, Leiden J M. An essential role for nuclear factor kappaB in promoting doublepositive thymocyte apoptosis. J Exp Med, 1999, 189(1): 145―158 doi: 10.1084/jem.189.1.145
Tak P P, Firestein G S. NF-kappaB: a key role ininflammatory diseases. J Clin Invest, 2001, 107(1): 7―11 doi: 10.1172/JCI11830
Lu H, Ouyang W, Huang C. Inflammation, a key event in cancer development. Mol Cancer Res, 2006, 4(4): 221―233 doi: 10.1158/1541-7786.MCR-05-0261
Neurath M F, Fuss I, Schürmann G, Pettersson S, Arnold K, Müller-Lobeck H, Strober W, Herfarth C, Büschenfelde K H. Cytokine gene transcription by NF-kappaB family members in patients with inflammatory bowel disease. Ann N Y Acad Sci, 1998, 859: 149―159 doi: 10.1111/j.1749-6632.1998.tb11119.x
Li Z, Zhang de K, Yi W Q, Ouyang Q, Chen Y Q, Gan H T. NF-kappaB p65 antisense oligonucleotides may serve asa novel molecular approach for the treatment of patients with ulcerativecolitis. Arch Med Res, 2008, 39(8): 729―734 doi: 10.1016/j.arcmed.2008.08.001
Yang J, Stark G R. Roles of unphosphorylatedSTATs in signaling. Cell Res, 2008, 18(4): 443―451 doi: 10.1038/cr.2008.41
Mudter J, Weigmann B, Bartsch B, Kiesslich R, Strand D, Galle P R, Lehr H A, Schmidt J, Neurath M F. Activation pattern of signal transducers and activators of transcription(STAT) factors in inflammatory bowel diseases. Am J Gastroenterol, 2005, 100(1): 64―72 doi: 10.1111/j.1572-0241.2005.40615.x
Hebenstreit D, Wirnsberger G, Horejs-Hoeck J, Duschl A. Signalingmechanisms, interaction partners, and target genes of STAT6. Cytokine Growth Factor Rev, 2006, 17(3): 173―188 doi: 10.1016/j.cytogfr.2006.01.004
Schindler C, Levy D E, Decker T. JAK-STAT signaling: from interferons to cytokines. J Biol Chem, 2007, 282(28): 20059―20063 doi: 10.1074/jbc.R700016200