cDNA array analysis of cytokines, chemokines, and receptors involved in the development of tnbs-induced colitis: Homeostatic role of VIP
Catalina Abad PhD
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorYasmina Juarranz
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorCarmen Martinez
Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain
Search for more papers by this authorAlicia Arranz
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorFlorencia Rosignoli PhD
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorMaría García-Gómez
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorJavier Leceta
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorCorresponding Author
Rosa P Gomariz
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Department of Cell Biology, Faculty of Biology, Complutense University, 28040 Madrid, SpainSearch for more papers by this authorCatalina Abad PhD
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorYasmina Juarranz
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorCarmen Martinez
Department of Cell Biology, Faculty of Medicine, Complutense University, Madrid, Spain
Search for more papers by this authorAlicia Arranz
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorFlorencia Rosignoli PhD
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorMaría García-Gómez
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorJavier Leceta
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Search for more papers by this authorCorresponding Author
Rosa P Gomariz
Department of Cell Biology, Faculty of Biology, Complutense University, Madrid, Spain
Department of Cell Biology, Faculty of Biology, Complutense University, 28040 Madrid, SpainSearch for more papers by this authorAbstract
Crohn's disease (CD) is a chronic inflammatory pathology of the intestine, characterized by diarrhea and weight loss. A healing effect of vasoactive intestinal peptide (VIP) in the murine model of CD based on 2,4,6-trinitrobencene sulfonic acid (TNBS) administration has been previously shown. The aim of this work was to analyze the expression of several mediators related to the inflammatory cascade in colitic and VIP-treated animals. With this aim, mice received either only TNBS or TNBS and VIP treatment on alternate days. cDNA microarray analysis and real-time polymerase chain reaction were performed on total mRNA from colon to study the expression of a battery of proinflammatory molecules such as the enzyme COX-2, the chemokines CX3CL1, CXCL12, CXCL13, CXCL14, CCR5, and CXCR2, and the cytokines interleukin (IL)-1β, IL-12, IL-18, IL-10, interferon-γ, and IL-4. TNBS administration induced the expression of all the proinflammatory mediators studied, whereas VIP treatment reduced their levels, increasing the anti-inflammatory IL-10 and the TH2 cytokine IL-4, explaining its beneficial action through inhibition of the inflammatory/TH1 response. These data describe not only the relation of several proinflammatory mediators to the development of TNBS colitis, reporting their time-course, but also show the beneficial action of VIP in this model through complete blockage of the inflammatory cascade and recovery of the colon homeostasis, providing a potential new alternative for CD therapy.
References
- 1 Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003; 3: 521–533.
- 2 Neurath MF, Fuss I, Kelsall BL, et al. Antibodies to interleukin 12 abrogate established experimental colitis in mice. J Exp Med. 1995; 1: 1281–1290.
- 3 Egan LJ, Sandborn WJ. Advances in the treatment of Crohn's disease. Gastroenterology. 2004; 126: 1574–1581.
- 4 Shanahan F. Crohn's disease. Lancet. 2002; 5: 62–69.
- 5 Delgado M, Pozo D, Ganea D. The significance of vasoactive intestinal Peptide in immunomodulation. Pharmacol Rev. 2004; 56: 249–290.
- 6 Gomariz RP, Martinez C, Abad C, et al. Immunology of VIP: a review and therapeutical perspectives. Curr Pharm Des. 2001; 7: 89–111.
- 7 Delgado M, Abad C, Martinez C, et al. Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases. J Mol Med. 2002; 80: 16–24.
- 8 Abad C, Martinez C, Juarranz MG, et al. Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn's disease. Gastroenterology. 2003; 124: 961–971.
- 9 Bustin SA. Absolute quantification of mRNA using real-time reverse transcription polymerase chain reaction assays. J Mol Endocrinol. 2000; 25: 169–193.
- 10 Rot A, von Andrian UH. Chemokines in innate and adaptive host defense: basic chemokinese grammar for immune cells. Annu Rev Immunol. 2004; 22: 891–928.
- 11 Maurer M, von Stebut E. Macrophage inflammatory protein-1. Int J Biochem Cell Biol. 2004; 36: 1882–1886.
- 12 Ajuebor MN, Zagorski J, Kunkel SL, et al. Contrasting roles for CXCR2 during experimental colitis. Exp Mol Pathol. 2004; 76: 1–8.
- 13 Laing KJ, Secombes CJ. Chemokines. DevComp Immunol. 2004; 28: 443–460.
- 14 Dale M, Nicklin MJ. Interleukin-1 receptor cluster: gene organization of ILR2, ILR1, IL1RL2 (IL-1Rrp2), IL1RL1 (T1/ST2), and IL-18R1 (IL-1Rrp) on human chromosome 2q. Genomics. 1999; 57: 177–179.
- 15 Nelson BH. IL-2, regulatory T cells, and tolerance. J Immunol. 2004; 172: 3983–3988.
- 16 Ito H. IL-6 and Crohn's disease. Curr Drug Targets Inflamm Allergy. 2003; 2: 125–130.
- 17 Holub MC, Mako E, Devay T, et al. Increased interleukin-6 levels, interleukin-6 receptor and gp130 expression in peripheral lymphocytes of patients with inflammatory bowel disease. Scand J Gastroenterol Suppl. 1998; 228: 47–50.
- 18 Liu Z, Geboes K, Colpaert S, et al. IL-15 is highly expressed in inflammatory bowel disease and regulates local T cell-dependent cytokine production. J Immunol. 2000; 164: 3608–3615.
- 19 Moseley TA, Haudenschild DR, Rose L, et al. Interleukin-17 family and IL-17 receptors. Cytokine Growth Factor Rev. 2003; 14: 155–174.
- 20
Witowski J,
Ksiazek K,
Jorres A.
Interleukin-17: a mediator of inflammatory responses.
Cell Mol Life Sci.
2004;
61:
567–579.
10.1002/(SICI)1522-2683(20000201)21:3<665::AID-ELPS665>3.0.CO;2-U CAS PubMed Web of Science® Google Scholar
- 21 Li H, Chen J, Huang A, et al. Cloning and characterization of IL-17B and IL-17C, two new members of the IL-17 cytokine family. Proc Natl Acad Sci USA. 2000; 97: 773–778.
- 22 Collins M, Whitters MJ, Young DA. IL-21 and IL-21 receptor: a new cytokine pathway modulates innate and adaptive immunity. Immunol Res. 2003; 28: 131–140.
- 23 Fort MM, Cheung J, Yen D, et al. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2001; 15: 985–995.
- 24 Howarth GS, Shoubridge CA. Enhancement of intestinal growth and repair by growth factors. Curr Opin Pharmacol. 2001; 1: 568–574.
- 25 Dinarello CA. Pro-inflammatory cytokines. Chest. 2000; 118: 503–508.
- 26 Weninger W, Carlsen HS, Goodarzi M, et al. Naïve T cell recruitment to nonlymphoid tissues: a role for endothelium-expressed CC chemokine ligand 21 in autoimmune disease and lymphoid neogenesis. J Immunol. 2003; 170: 4638–4648.
- 27 Varona R, Cadenas V, Flores J, et al. CCR6 has a non-redundant role in the development of inflammatory bowel disease. Eur J Immunol. 2003; 33: 2937–2946.
- 28 Luster AD. The role of chemokines in linking innate and adaptive immunity. Curr Opin Immunol. 2002; 14: 129–135.
- 29 Moser B, Schaerli P, Loetscher P. CXCR5+ T cells: follicular homing takes center stage in T-helper-cell responses. Trends Immunol. 2002; 23: 250–254.
- 30 Moser B, Wolf M, Walz A, et al. Chemokines: multiple levels of leukocyte migration control. Trends Immunol. 2004; 25: 75–84.
- 31 Muller G, Hopken UE, Lipp M. The impact of CCR7 and CXCR5 on lymphoid organ development and systemic immunity. Immunol Rev. 2003; 195: 117–135.
- 32 Muller G, Lipp M. Shaping up adaptive immunity: the impact of CCR7 and CXCR5 on lymphocyte trafficking. Microcirculation. 2003; 10: 325–334.
- 33 Obermeier F, Schwarz H, Dunger N, et al. OX40/OX40L interaction induces the expression of CXCR5 and contributes to chronic colitis induced by dextran sulfate sodium in mice. Eur J Immunol. 2003; 33: 3265–3274.
- 34 Carlsen HS, Baekkevold ES, Morton HC, et al. Monocyte-like and mature macrophages produce CXCL13 (B-cell-attracting chemokine 1) in inflammatory lesions with lymphoid neogenesis. Blood. 2004; 104: 3021–3027.
- 35 Jo Y, Matsumoto T, Yada S, et al. CCR4 is an up-regulated chemokine receptor of peripheral blood memory CD4+ T cells in Crohn's disease. Clin Exp Immunol. 2003; 132: 332–338.
- 36 Papadakis KA, Landers C, Prehn J, et al. CC chemokine receptor 9 expression defines a subset of peripheral blood lymphocytes with mucosal T cell phenotype and Th1 or T-regulatory 1 cytokine profile. J Immunol. 2003; 171: 159–165.
- 37 Romagnani P, Lasagni L, Annunziato F, et al. CXC chemokines: the regulatory link between inflammation and angiogenesis. Trends Immunol. 2004; 25: 201–209.
- 38 Watford WT, Moriguchi M, Morinobu A, et al. The biology of IL-12: coordinating innate and adaptive immune responses. Cytokine Growth Factor Rev. 2003; 14: 361–368.
- 39 Parnet P, Garka KE, Bonnert TP, et al. IL-1Rrp is a novel receptor-like molecule similar to the type I interleukin-1 receptor and its homologues T1/ST2 and IL-1R AcP. J Biol Chem. 1996; 271: 3967–3970.
- 40 Monteleone G, Trapasso F, Parrello T, et al. Bioactive IL-18 expression is up-regulated in Crohn's disease. J Immunol. 1999; 163: 143–147.
- 41 Camoglio L, Te Velde AA, Tigges AJ, et al. Altered expresión of interferon-gamma and interleukin-4 in inflammatory bowel disease. Inflamm Bowel Dis. 1998; 4: 285–290.
- 42 Kitamura K, Nakamoto Y, Kaneko S, et al. Pivotal roles of interleukin-6 in transmural inflammation in murine T cell transfer colitis. J Leukoc Biol. 2004; 76: 1111–1117.
- 43 Maerten P, Shen C, Colpaert S, et al. Involvement of interleukin 18 in Crohn's disease: evidence from in vitro analysis of human gut inflammatory cells and from experimental colitis models. Clin Exp Immunol. 2004; 135: 310–317.
- 44 Schreiber S, Nikolaus S, Hampe J, et al. Tumour necrosis factor alpha and interleukin 1beta in relapse of Crohn's disease. Lancet. 1999; 353: 459–461.
- 45 Pallone F, Monteleone G. Interleukin 12 and Th1 responses in inflammatory bowel disease. Gut. 1998; 43: 735–736.
- 46 McCormack G, Moriarty D, O'Donoghue DP, et al. Tissue cytokine and chemokine expression in inflammatory bowel disease. Inflamm Res. 2001; 50: 491–495.
- 47 Papadakis KA. Chemokines in inflammatory bowel disease. Curr Allergy Asthma Rep. 2004; 4: 83–89.
- 48 Newman R, Cuan N, Hampartzoumian T, et al. Vasoactive intestinal peptide impairs leukocyte migration but fails to modify experimental murine colitis. Clin Exp Immunol. 2005; 139: 411–420.
- 49 Elson CO, Sartor RB, Tennyson GS, et al. Experimental models of inflammatory bowel disease. Gastroenterology. 1995; 109: 1344–1367.
- 50 Liu H, Pope RM. Phagocytes: mechanisms of inflammation and tissue destruction. Rheum Dis Clin North Am. 2004; 30: 19–39.
- 51 Stallmach A, Giese T, Schmidt C, et al. Cytokine/chemokine transcript profiles reflect mucosal inflammation in Crohn's disease. Int J Colorectal Dis. 2004; 19: 308–315.
- 52 Sun FF, Lai PS, Yue G, et al. Pattern of cytokine and adhesion molecule mRNA in hapten-induced relapsing colon inflammation in the rat. Inflammation. 2001; 25: 33–45.
- 53 Hendel J, Nielsen OH. Expression of cyclooxygenase-2 mRNA in active inflammatory bowel disease. Am J Gastroenterol. 1997; 92: 1170–1173.
- 54 Khan I, Al-Awadi FM, Thomas N, et al. Cyclooxygenase-2 inhibition and experimental colitis: beneficial effects of phosphorothioated antisense oligonucleotide and meloxicam. Scand J Gastroenterol. 2002; 37: 1428–1436.
- 55 Dinarello CA. The IL-1 family and inflammatory diseases. Clin Exp Rheumatol. 2002; 20: S1–13.
- 56 Warner TD, Mitchell JA. Cyclooxygenases: new forms, new inhibitors, and lessons from the clinic. FASEB J. 2004; 18: 790–804.
- 57 Claria J. Cyclooxygenase-2 biology. Curr Pharm Des. 2003; 9: 2177–2190.
- 58 Delgado M, Martinez C, Pozo D, et al. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activation polypeptide (PACAP) protect mice from lethal endotoxemia through the inhibition of TNF-alpha and IL-6. J Immunol. 1999; 162: 1200–1205.
- 59 Delgado M, Abad C, Martinez C, et al. Vasoactive intestinal peptide prevents experimental arthritis by downregulating both autoimmune and inflammatory components of the disease. Nat Med. 2001; 7: 563–568.
- 60 Neurath M, Fuss I, Strober W. TNBS-colitis. Int Rev Immunol. 2000; 19: 51–62.
- 61 Bamias G, Sugawara K, Pagnini C, et al. The Th1 immune pathway as a therapeutic target in Crohn's disease. Curr Opin Investig Drugs. 2003; 4: 1279–1286.
- 62 Schroder K, Hertzog PJ, Ravasi T, et al. Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol. 2004; 75: 163–189.
- 63 Blaschke S, Koziolek M, Schwarz A, et al. Pro-inflammatory role of fractalkine (CX3CL1) in rheumatoid arthritis. J Rheumatol. 2003; 30: 1918–1927.
- 64 Muehlhoefer A, Saubermann LJ, Gu X, et al. Fractalkine is an epithelial and endothelial cell-derived chemoattractant for intraepithelial lymphocytes in the small intestinal mucosa. J Immunol. 2000; 164: 3368–3376.
- 65 Rector A, Vermeire S, Thoelen I, et al. Analysis of the CC chemokine receptor 5 (CCR5) delta-32 polymorphism in inflammatory bowel disease. Hum Genet. 2001; 108: 190–193.
- 66 Bouma G, Strober W. The immunological and genetic basis of inflammatory bowel disease. Nat Rev Immunol. 2003; 3: 521–533.
- 67 Maerten P, Shen C, Colpaert S, et al. Involvement of interleukin 18 in Crohn's disease: evidence from in vitro analysis of human gut inflammatory cells and from experimental colitis models. Clin Exp Immunol. 2004; 135: 310–317.
- 68 Stallmach A, Marth T, Weiss B, et al. An interleukin 12 p40-IgG2b fusion protein abrogates T cell mediated inflammation: anti-inflammatory activity in Crohn's disease and experimental colitis in vivo. Gut. 2004; 53: 339–345.
- 69 Gounni AS, Hamid Q, Rahman SM, et al. IL-9-mediated induction of eotaxin1/CCL11 in human airway smooth muscle cells. J Immunol. 2004; 173: 2771–2779.
- 70 Grimm MC, Newman R, Hassim Z, et al. Vasoactive intestinal peptide acts as a potent suppressor of inflammation in vivo by trans-deactivating chemokine receptors. J Immunol. 2003; 171: 4990–4994.
- 71 Delgado M. VIP: a very important peptide in T helper differentiation. Trends Immunol. 2003; 24: 221–224.
- 72 Hunter MM, McKay DM. Review article: helminths as therapeutic agents for inflammatory bowel disease. Aliment Pharmacol Ther. 2004; 19: 167–177.
- 73 Ruddle NH. Lymphoid neo-organogenesis: lymphotoxin's role in inflammation and development. Immunol Res. 1999; 19: 119–125.
- 74 Hjelmstrom P. Lymphoid neogenesis: de novo formation of lymphoid tissue in chronic inflammation through expression of homing chemokines. J Leukoc Biol. 2001; 69: 331–339.
- 75 Pablos JL, Santiago B, Galindo M, et al. Synoviocyte-derived CXCL12 is displayed on endothelium and induces angiogenesis in rheumatoid arthritis. J Immunol. 2003; 170: 2147–2152.