Activation of histamine H4 receptor inhibits TNFα/IMD-0354-induced apoptosis in human salivary NS-SV-AC cells
Tóm tắt
Apoptosis is involved in the pathogenesis of Sjögren’s syndrome (SS), an autoimmune disease affecting exocrine glands. Our recent studies revealed diminished histamine H4 receptor (H4R) expression and impaired histamine transport in the salivary gland epithelial cells in SS. The aim was now to test if nanomolar histamine and high-affinity H4R signaling affect apoptosis of human salivary gland epithelial cell. Simian virus 40-immortalized acinar NS-SV-AC cells were cultured in serum-free keratinocyte medium ± histamine H4R agonist HST-10. Expression and internalization of H4R were studied by immunofluorescence staining ± clathrin inhibitor methyl-β-cyclodextrin (MβCD). Apoptosis induced using tumor necrosis factor-α with nuclear factor-κB inhibitor IMD-0354 was studied using phase contrast microscopy, Western blot, flow cytometry and polymerase chain reaction (qRT-PCR). HST-10-stimulated H4R internalization was inhibited by MβCD. Western blotting revealed diminished phosphorylated c-Jun N-terminal kinase JNK, but unchanged levels of phosphorylated extracellular signal regulated kinase pERK1/2 in H4R-stimulated samples compared to controls. qRT-PCR showed up-regulated expression of anti-apoptotic B cell lymphoma-extra large/Bcl-xL mRNAs and proteins, whereas pro-apoptotic Bcl-2-associated X protein/BAX remained unchanged in H4R-stimulated samples. H4R stimulation diminished cleavage of PARP and flow cytometry showed significant dose-dependent inhibitory effect of H4R stimulation on apoptosis. As far as we know this is the first study showing inhibitory effect of H4R activation on apoptosis of human salivary gland cells. Diminished H4R-mediated activation may contribute to loss of immune tolerance in autoimmune diseases and in SS in particular.
Tài liệu tham khảo
Moutsopoulos HM (2007) Sjogren’s syndrome or autoimmune epithelitis? Clin Rev Allergy Immunol 32(3):199–200. doi:10.1007/s12016-007-8042-1
Kong L, Ogawa N, Nakabayashi T, Liu GT, D’Souza E, McGuff HS, Guerrero D, Talal N, Dang H (1997) Fas and Fas ligand expression in the salivary glands of patients with primary Sjogren’s syndrome. Arthritis Rheum 40(1):87–97
Herrera-Esparza R, Bollain-y-Goytia J, Ruvalcaba C, Ruvalcaba M, Pacheco-Tovar D, Avalos-Diaz E (2008) Apoptosis and cell proliferation: the paradox of salivary glands in Sjogren’s disease. Acta Reumatologica Portuguesa 33(3):299–303
Fox PC, Brennan M, Di Sun P (1999) Cytokine expression in human labial minor salivary gland epithelial cells in health and disease. Arch Oral Biol 44(Suppl 1):S49–S52
Kyriakidis NC, Kapsogeorgou EK, Tzioufas AG (2014) A comprehensive review of autoantibodies in primary Sjogren’s syndrome: clinical phenotypes and regulatory mechanisms. J Autoimmun 51:67–74. doi:10.1016/j.jaut.2013.11.001
Wu AJ, Chen ZJ, Tsokos M, O’Connell BC, Ambudkar IS, Baum BJ (1996) Interferon-gamma induced cell death in a cultured human salivary gland cell line. J Cell Physiol 167(2):297–304. doi:10.1002/(SICI)1097-4652(199605)167:2
Abu-Helu RF, Dimitriou ID, Kapsogeorgou EK, Moutsopoulos HM, Manoussakis MN (2001) Induction of salivary gland epithelial cell injury in Sjogren’s syndrome: in vitro assessment of T cell-derived cytokines and Fas protein expression. J Autoimmun 17(2):141–153. doi:10.1006/jaut.2001.0524
Ohlsson M, Jonsson R, Brokstad KA (2002) Subcellular redistribution and surface exposure of the Ro52, Ro60 and La48 autoantigens during apoptosis in human ductal epithelial cells: a possible mechanism in the pathogenesis of Sjogren’s syndrome. Scand J Immunol 56(5):456–469
Nagaraju K, Cox A, Casciola-Rosen L, Rosen A (2001) Novel fragments of the Sjogren’s syndrome autoantigens alpha-fodrin and type 3 muscarinic acetylcholine receptor generated during cytotoxic lymphocyte granule-induced cell death. Arthritis Rheum 44(10):2376–2386
Liu F, Bardhan K, Yang D, Thangaraju M, Ganapathy V, Waller JL, Liles GB, Lee JR, Liu K (2012) NF-kappaB directly regulates Fas transcription to modulate Fas-mediated apoptosis and tumor suppression. J Biol Chem 287(30):25530–25540. doi:10.1074/jbc.M112.356279
Inazawa J, Itoh N, Abe T, Nagata S (1992) Assignment of the human Fas antigen gene (Fas) to 10q24.1. Genomics 14(3):821–822
Lee EW, Seo J, Jeong M, Lee S, Song J (2012) The roles of FADD in extrinsic apoptosis and necroptosis. BMB reports 45(9):496–508
Wajant H, Pfizenmaier K, Scheurich P (2003) Tumor necrosis factor signaling. Cell Death Differ 10(1):45–65. doi:10.1038/sj.cdd.4401189
Chen G, Goeddel DV (2002) TNF-R1 signaling: a beautiful pathway. Science 296(5573):1634–1635. doi:10.1126/science.1071924
Medina VA, Prestifilippo JP, Croci M, Carabajal E, Bergoc RM, Elverdin JC, Rivera ES (2011) Histamine prevents functional and morphological alterations of submandibular glands induced by ionising radiation. Int J Radiat Biol 87(3):284–292. doi:10.3109/09553002.2010.533247
Carabajal E, Massari N, Croci M, Martinel Lamas DJ, Prestifilippo JP, Bergoc RM, Rivera ES, Medina VA (2012) Radioprotective potential of histamine on rat small intestine and uterus. Eur J Histochem 56(4):e48. doi:10.4081/ejh.2012.e48
Seifert R, Schneider EH, Dove S, Brunskole I, Neumann D, Strasser A, Buschauer A (2011) Paradoxical stimulatory effects of the “standard” histamine H4-receptor antagonist JNJ7777120: the H4 receptor joins the club of 7 transmembrane domain receptors exhibiting functional selectivity. Mol Pharmacol 79(4):631–638. doi:10.1124/mol.111.071266
Martinel Lamas DJ, Carabajal E, Prestifilippo JP, Rossi L, Elverdin JC, Merani S, Bergoc RM, Rivera ES, Medina VA (2013) Protection of radiation-induced damage to the hematopoietic system, small intestine and salivary glands in rats by JNJ7777120 compound, a histamine H4 ligand. PLoS ONE 8(7):e69106. doi:10.1371/journal.pone.0069106
Prestifilippo JP, Carabajal E, Croci M, Fernandez-Solari J, Rivera ES, Elverdin JC, Medina VA (2012) Histamine modulates salivary secretion and diminishes the progression of periodontal disease in rat experimental periodontitis. Inflamm Res 61(5):455–464. doi:10.1007/s00011-011-0432-4
Stegaev V, Sillat T, Porola P, Hanninen A, Falus A, Mieliauskaite D, Buzas E, Rotar Z, Mackiewicz Z, Stark H, Chazot PL, Konttinen YT (2012) Brief report: first identification of H(4) histamine receptor in healthy salivary glands and in focal sialadenitis in Sjogren’s syndrome. Arthritis Rheum 64(8):2663–2668. doi:10.1002/art.34484
Thurmond RL, Gelfand EW, Dunford PJ (2008) The role of histamine H1 and H4 receptors in allergic inflammation: the search for new antihistamines. Nat Rev Drug Discov 7(1):41–53. doi:10.1038/nrd2465
Tiligada E, Zampeli E, Sander K, Stark H (2009) Histamine H3 and H4 receptors as novel drug targets. Expert Opin Investig Drugs 18(10):1519–1531. doi:10.1517/14728220903188438
Stegaev V, Nies AT, Porola P, Mieliauskaite D, Sanchez-Jimenez F, Urdiales JL, Sillat T, Schwelberger HG, Chazot PL, Katebe M, Mackiewicz Z, Konttinen YT, Nordstrom DC (2013) Histamine transport and metabolism are deranged in salivary glands in Sjogren’s syndrome. Rheumatology (Oxford) 52(9):1599–1608. doi:10.1093/rheumatology/ket188
Kejr A, Gigante C, Hames V, Krieg C, Mages J, Konig N, Kalus J, Schudmann K, Diel F (2010) Receptive music therapy and salivary histamine secretion. Inflamm Res 59(Suppl 2):S217–S218. doi:10.1007/s00011-009-0145-0
Yamatodani A, Fukuda H, Wada H, Iwaeda T, Watanabe T (1985) High-performance liquid chromatographic determination of plasma and brain histamine without previous purification of biological samples: cation-exchange chromatography coupled with post-column derivatization fluorometry. J Chromatogr 344:115–123
Azuma M, Tamatani T, Kasai Y, Sato M (1993) Immortalization of normal human salivary gland cells with duct-, myoepithelial-, acinar-, or squamous phenotype by transfection with SV40 ori- mutant deoxyribonucleic acid. Lab Invest 69(1):24–42
Kottke T, Sander K, Weizel L, Schneider EH, Seifert R, Stark H (2011) Receptor-specific functional efficacies of alkyl imidazoles as dual histamine H3/H4 receptor ligands. Eur J Pharmacol 654(3):200–208. doi:10.1016/j.ejphar.2010.12.033
Laemmli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227(5259):680–685
Ohtani Y, Irie T, Uekama K, Fukunaga K, Pitha J (1989) Differential effects of alpha-, beta- and gamma-cyclodextrins on human erythrocytes. Eur J Biochem FEBS 186(1–2):17–22
Neufeld EB, Cooney AM, Pitha J, Dawidowicz EA, Dwyer NK, Pentchev PG, Blanchette-Mackie EJ (1996) Intracellular trafficking of cholesterol monitored with a cyclodextrin. J Biol Chem 271(35):21604–21613
Alwin Prem Anand A, Gowri Sankar S, Kokila Vani V (2012) Immortalization of neuronal progenitors using SV40 large T antigen and differentiation towards dopaminergic neurons. J Cell Mol Med 16(11):2592–2610. doi:10.1111/j.1582-4934.2012.01607.x
Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, Green DR (2004) Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science 303(5660):1010–1014. doi:10.1126/science.1092734
Lee JY, Lee SB, Park WY, Choi YJ, Kim B, Kim YH, Jun DY, Kim YH (2014) Tumor suppressor protein p53 promotes 2-methoxyestradiol-induced activation of Bak and Bax, leading to mitochondria-dependent apoptosis in human colon cancer HCT116 cells. J Microbiol Biotechnol [Epub ahead of print]
Vogel S, Raulf N, Bregenhorn S, Biniossek ML, Maurer U, Czabotar P, Borner C (2012) Cytosolic Bax: does it require binding proteins to keep its pro-apoptotic activity in check? J Biol Chem 287(12):9112–9127. doi:10.1074/jbc.M111.248906
Hayashi Y, Arakaki R, Ishimaru N (2004) Apoptosis and estrogen deficiency in primary Sjogren syndrome. Curr Opin Rheumatol 16(5):522–526
Segerberg-Konttinen M, Bergroth V, Jungell P, Malmstrom M, Nordstrom D, Sane J, Immonen I, Konttinen YT (1987) T lymphocyte activation state in the minor salivary glands of patients with Sjogren’s syndrome. Ann Rheum Dis 46(9):649–653
Konttinen YT, Kemppinen P, Koski H, Li TF, Jumppanen M, Hietanen J, Santavirta S, Salo T, Larsson A, Hakala M, Sorsa T (1999) T(H)1 cytokines are produced in labial salivary glands in Sjogren’s syndrome, but also in healthy individuals. Scand J Rheumatol 28(2):106–112
Mitsias DI, Tzioufas AG, Veiopoulou C, Zintzaras E, Tassios IK, Kogopoulou O, Moutsopoulos HM, Thyphronitis G (2002) The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of Sjogren’s syndrome. Clin Exp Immunol 128(3):562–568
Mavragani CP, Moutsopoulos HM (2014) Sjogren’s syndrome. Annu Rev Pathol 9:273–285. doi:10.1146/annurev-pathol-012513-104728
Fujihara T, Fujita H, Tsubota K, Saito K, Tsuzaka K, Abe T, Takeuchi T (1999) Preferential localization of CD8+ alpha E beta 7+ T cells around acinar epithelial cells with apoptosis in patients with Sjogren’s syndrome. J Immunol 163(4):2226–2235
Konttinen YT, Tuominen S, Segerberg-Konttinen M, Jungell P, Malmstrom MJ, Gronblad M, Guven O, Santavirta S, Panula P (1990) Mast cells in the labial salivary glands of patients with Sjogren’s syndrome: a histochemical, immunohistochemical, and electron microscopical study. Ann Rheum Dis 49(9):685–689
Salem A, Al-Samadi A, Stegajev V, Stark H, Häyrinen-Immonen R, Ainola M, Heitanen J, Konttinen YT (2014) Histamine H4 Receptor in Oral Lichen Planus. Oral Dis. doi:10.1111/odi.12290
Luttrell LM, Lefkowitz RJ (2002) The role of beta-arrestins in the termination and transduction of G-protein-coupled receptor signals. J Cell Sci 115(Pt 3):455–465
Krueger KM, Daaka Y, Pitcher JA, Lefkowitz RJ (1997) The role of sequestration in G protein-coupled receptor resensitization. Regulation of beta2-adrenergic receptor dephosphorylation by vesicular acidification. J Biol Chem 272(1):5–8
Rodal SK, Skretting G, Garred O, Vilhardt F, van Deurs B, Sandvig K (1999) Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles. Mol Biol Cell 10(4):961–974
Leff P (1995) The two-state model of receptor activation. Trends Pharmacol Sci 16(3):89–97
Boucher MJ, Morisset J, Vachon PH, Reed JC, Laine J, Rivard N (2000) MEK/ERK signaling pathway regulates the expression of Bcl-2, Bcl-X(L), and Mcl-1 and promotes survival of human pancreatic cancer cells. J Cell Biochem 79(3):355–369
Ola MS, Nawaz M, Ahsan H (2011) Role of Bcl-2 family proteins and caspases in the regulation of apoptosis. Mol Cell Biochem 351(1–2):41–58. doi:10.1007/s11010-010-0709-x