Smoking decreases the response of human lung macrophages to double-stranded RNA by reducing TLR3 expression

Respiratory Research

Jeffrey L Curtis²  James M Beck²  Stephen W Chensue¹  Fernando J Martinez⁴  Alexandra L McCubbrey⁵  Theresa M Ames⁴  Joanne Sonstein⁴  Jeanette P Brown⁴  Christine M Freeman³  Jill C Todt⁴ 

[1] Pathology & Laboratory Medicine Service, Department of Veterans Affairs Health Care System, Ann Arbor, MI, 48105-2303, USA;Pulmonary & Critical Care Medicine Section, Medical Service, Department of Veterans Affairs Health Care System, 2215 Fuller Road, Ann Arbor, MI, 48105-2303, USA;Research Service, Department of Veterans Affairs Health Care System, Ann Arbor, MI, 48105-2303, USA;Division of Pulmonary & Critical Care Medicine, Department of Internal Medicine, University of Michigan Health Care System, Ann Arbor, MI, 48109-2399, USA;Graduate Program in Immunology, University of Michigan Health Care System, Ann Arbor, MI, 48109-2399, USA

关键词: Alveolar;    Macrophages;    Toll-like receptors;    Effects;    Cigarette smoking;    Lung;   

Others  :  794906
DOI  :  10.1186/1465-9921-14-33

 received in 2012-05-03, accepted in 2013-02-22,  发布年份 2013

【 摘 要 】

Background

Cigarette smoking is associated with increased frequency and duration of viral respiratory infections, but the underlying mechanisms are incompletely defined. We investigated whether smoking reduces expression by human lung macrophages (Mø) of receptors for viral nucleic acids and, if so, the effect on CXCL10 production.

Methods

We collected alveolar macrophages (AMø) by bronchoalveolar lavage of radiographically-normal lungs of subjects undergoing bronchoscopies for solitary nodules (n = 16) and of volunteers who were current or former smokers (n = 7) or never-smokers (n = 13). We measured expression of mRNA transcripts for viral nucleic acid receptors by real-time PCR in those AMø and in the human Mø cell line THP-1 following phorbol myristate acetate/vitamin D3 differentiation and exposure to cigarette smoke extract, and determined TLR3 protein expression using flow cytometry and immunohistochemistry. We also used flow cytometry to examine TLR3 expression in total lung Mø from subjects undergoing clinically-indicated lung resections (n = 25). Of these, seven had normal FEV1 and FEV1/FVC ratio (three former smokers, four current smokers); the remaining 18 subjects (14 former smokers; four current smokers) had COPD of GOLD stages I-IV. We measured AMø production of CXCL10 in response to stimulation with the dsRNA analogue poly(I:C) using Luminex assay.

Results

Relative to AMø of never-smokers, AMø of smokers demonstrated reduced protein expression of TLR3 and decreased mRNA for TLR3 but not TLR7, TLR8, TLR9, RIG-I, MDA-5 or PKR. Identical changes in TLR3 gene expression were induced in differentiated THP-1 cells exposed to cigarette smoke-extract in vitro for 4 hours. Among total lung Mø, the percentage of TLR3-positive cells correlated inversely with active smoking but not with COPD diagnosis, FEV1% predicted, sex, age or pack-years. Compared to AMø of never-smokers, poly(I:C)-stimulated production of CXCL10 was significantly reduced in AMø of smokers.

Conclusions

Active smoking, independent of COPD stage or smoking duration, reduces both the percent of human lung Mø expressing TLR3, and dsRNA-induced CXCL10 production, without altering other endosomal or cytoplasmic receptors for microbial nucleic acids. This effect provides one possible mechanism for increased frequency and duration of viral lower respiratory tract infections in smokers.

Trial registration

ClinicalTrials.gov NCT00281190, NCT00281203 and NCT00281229.

【 授权许可】

   
2013 Todt et al; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Johnston SL: Overview of virus-induced airway disease. Proc Am Thorac Soc 2005, 2:150-156.
• [2]Proud D, Chow CW: Role of viral infections in asthma and chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2006, 35:513-518.
• [3]Arcavi L, Benowitz NL: Cigarette smoking and infection. Arch Intern Med 2004, 164:2206-2216.
• [4]Aronson MD, Weiss ST, Ben RL, Komaroff AL: Association between cigarette smoking and acute respiratory tract illness in young adults. JAMA 1982, 248:181-183.
• [5]Bensenor IM, Cook NR, Lee IM, Chown MJ, Hennekens CH, Buring JE, Manson JE: Active and passive smoking and risk of colds in women. Ann Epidemiol 2001, 11:225-231.
• [6]Marcy TW, Merrill WW: Cigarette smoking and respiratory tract infection. Clin Chest Med 1987, 8:381-391.
• [7]Sopori M: Effects of cigarette smoke on the immune system. Nat Rev Immunol 2002, 2:372-377.
• [8]Mehta H, Nazzal K, Sadikot RT: Cigarette smoking and innate immunity. Inflamm Res 2008, 57:497-503.
• [9]Matsunaga K, Klein TW, Friedman H, Yamamoto Y: Involvement of nicotinic acetylcholine receptors in suppression of antimicrobial activity and cytokine responses of alveolar macrophages to Legionella pneumophila infection by nicotine. J Immunol 2001, 167:6518-6524.
• [10]Ouyang Y, Virasch N, Hao P, Aubrey MT, Mukerjee N, Bierer BE, Freed BM: Suppression of human IL-1beta, IL-2, IFN-gamma, and TNF-alpha production by cigarette smoke extracts. J Allergy Clin Immunol 2000, 106:280-287.
• [11]Wewers MD, Diaz PT, Wewers ME, Lowe MP, Nagaraja HN, Clanton TL: Cigarette smoking in HIV infection induces a suppressive inflammatory environment in the lung. Am J Respir Crit Care Med 1998, 158:1543-1549.
• [12]Chen H, Cowan MJ, Hasday JD, Vogel SN, Medvedev AE: Tobacco smoking inhibits expression of proinflammatory cytokines and activation of IL-1R-associated kinase, p38, and NF-kappaB in alveolar macrophages stimulated with TLR2 and TLR4 agonists. J Immunol 2007, 179:6097-6106.
• [13]Birrell MA, Wong S, Catley MC, Belvisi MG: Impact of tobacco-smoke on key signaling pathways in the innate immune response in lung macrophages. J Cell Physiol 2008, 214:27-37.
• [14]Edwards K, Braun KM, Evans G, Sureka AO, Fan S: Mainstream and sidestream cigarette smoke condensates suppress macrophage responsiveness to interferon gamma. Hum Exp Toxicol 1999, 18:233-240.
• [15]Matsumoto M, Funami K, Tanabe M, Oshiumi H, Shingai M, Seto Y, Yamamoto A, Seya T: Subcellular localization of Toll-like receptor 3 in human dendritic cells. J Immunol 2003, 171:3154-3162.
• [16]Orinska Z, Bulanova E, Budagian V, Metz M, Maurer M, Bulfone-Paus S: TLR3-induced activation of mast cells modulates CD8+ T-cell recruitment. Blood 2005, 106:978-987.
• [17]Meylan E, Tschopp J: Toll-like receptors and RNA helicases: two parallel ways to trigger antiviral responses. Mol Cell 2006, 22:561-569.
• [18]Matsukura S, Kokubu F, Kurokawa M, Kawaguchi M, Ieki K, Kuga H, Odaka M, Suzuki S, Watanabe S, Homma T: Role of RIG-I, MDA-5, and PKR on the expression of inflammatory chemokines induced by synthetic dsRNA in airway epithelial cells. Int Arch Allergy Immunol 2007, 143(Suppl 1):80-83.
• [19]Hui KP, Lee SM, Cheung CY, Ng IH, Poon LL, Guan Y, Ip NY, Lau AS, Peiris JS: Induction of proinflammatory cytokines in primary human macrophages by influenza A virus (H5N1) is selectively regulated by IFN regulatory factor 3 and p38 MAPK. J Immunol 2009, 182:1088-1098.
• [20]Dhillon N, Zhu X, Peng F, Yao H, Williams R, Qiu J, Callen S, Ladner AO, Buch S: Molecular mechanism(s) involved in the synergistic induction of CXCL10 by human immunodeficiency virus type 1 Tat and interferon-gamma in macrophages. J Neurovirol 2008, 14:196-204.
• [21]Livengood AJ, Wu CC, Carson DA: Opposing roles of RNA receptors TLR3 and RIG-I in the inflammatory response to double-stranded RNA in a Kaposi’s sarcoma cell line. Cell Immunol 2007, 249:55-62.
• [22]Michalec L, Choudhury BK, Postlethwait E, Wild JS, Alam R, Lett-Brown M, Sur S: CCL7 and CXCL10 orchestrate oxidative stress-induced neutrophilic lung inflammation. J Immunol 2002, 168:846-852.
• [23]Agostini C, Calabrese F, Poletti V, Marcer G, Facco M, Miorin M, Cabrelle A, Baesso I, Zambello R, Trentin L, Semenzato G: CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis. Respir Res 2005, 6:20. BioMed Central Full Text
• [24]Yuan J, Liu Z, Lim T, Zhang H, He J, Walker E, Shier C, Wang Y, Su Y, Sall A: CXCL10 inhibits viral replication through recruitment of natural killer cells in coxsackievirus B3-induced myocarditis. Circ Res 2009, 104:628-638.
• [25]Cole AM, Ganz T, Liese AM, Burdick MD, Liu L, Strieter RM: Cutting edge: IFN-inducible ELR- CXC chemokines display defensin-like antimicrobial activity. J Immunol 2001, 167:623-627.
• [26]Vasquez RE, Xin L, Soong L: Effects of CXCL10 on dendritic cell and CD4+ T-cell functions during Leishmania amazonensis infection. Infect Immun 2008, 76:161-169.
• [27]Freeman CM, Curtis JL, Chensue SW: CC chemokine receptor 5 and CXC chemokine receptor 6 expression by lung CD8+ cells correlates with chronic obstructive pulmonary disease severity. Am J Pathol 2007, 171:767-776.
• [28]Freeman CM, Han MK, Martinez FJ, Murray S, Liu LX, Chensue SW, Polak TJ, Sonstein J, Todt JC, Ames TM: Cytotoxic potential of lung CD8(+) T cells increases with chronic obstructive pulmonary disease severity and with in vitro stimulation by IL-18 or IL-15. J Immunol 2010, 184:6504-6513.
• [29]McCubbrey AL, Sonstein J, Ames TM, Freeman CM, Curtis JL: Glucocorticoids relieve collectin-driven suppression of apoptotic cell uptake in murine alveolar macrophages through downregulation of SIRPalpha. J Immunol 2012, 189:112-119.
• [30]Koarai A, Yanagisawa S, Sugiura H, Ichikawa T, Akamatsu K, Hirano T, Nakanishi M, Matsunaga K, Minakata Y, Ichinose M: Cigarette smoke augments the expression and responses of toll-like receptor 3 in human macrophages. Respirology 2012, 17:1018-1025.
• [31]Seemungal T, Harper-Owen R, Bhowmic A, Moric I, Sanderson G, Message S, MacCallum P, Meade T, Jeffries D, Johnston S, Wedzicha J: Respiratory viruses, symptoms, and inflammatory markers in acute exacerbations and stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2001, 164:1618-1623.
• [32]Papi A, Bellettato C, Braccioni F, Romagnoli M, Casolari P, Caramori G, Fabbri L, Johnston S: Infections and airway inflammation in chronic obstructive pulmonary disease severe exacerbations. Am J Respir Crit Care Med 2006, 173:1114-1121.
• [33]Nicholson KG, Kent J, Ireland DC: Respiratory viruses and exacerbations of asthma in adults. BMJ 1993, 307:982-986.
• [34]Johnston SL, Pattemore PK, Sanderson G, Smith S, Lampe F, Josephs L, Symington P, O’Toole S, Myint SH, Tyrrell DA: Community study of role of viral infections in exacerbations of asthma in 9–11 year old children. BMJ 1995, 310:1225-1229.
• [35]Johnston SL, Pattemore PK, Sanderson G, Smith S, Campbell MJ, Josephs LK, Cunningham A, Robinson BS, Myint SH, Ward ME: The relationship between upper respiratory infections and hospital admissions for asthma: a time-trend analysis. Am J Respir Crit Care Med 1996, 154:654-660.
• [36]Kanner RE, Anthonisen NR, Connett JE: Lower respiratory illnesses promote FEV(1) decline in current smokers but not ex-smokers with mild chronic obstructive pulmonary disease: results from the lung health study. Am J Respir Crit Care Med 2001, 164:358-364.
• [37]Thomson NC, Chaudhuri R: Asthma in smokers: challenges and opportunities. Curr Opin Pulm Med 2009, 15:39-45.
• [38]Eisner MD, Iribarren C: The influence of cigarette smoking on adult asthma outcomes. Nicotine Tob Res 2007, 9:53-56.
• [39]Sippel JM, Pedula KL, Vollmer WM, Buist AS, Osborne ML: Associations of smoking with hospital-based care and quality of life in patients with obstructive airway disease. Chest 1999, 115:691-696.
• [40]Siroux V, Pin I, Oryszczyn MP, LeMoual N, Kauffmann F: Relationships of active smoking to asthma and asthma severity in the EGEA study. Epidemiological study on the Genetics and Environment of Asthma. Eur Respir J 2000, 15:470-477.
• [41]Lazarus SC, Chinchilli VM, Rollings NJ, Boushey HA, Cherniack R, Craig TJ, Deykin A, DiMango E, Fish JE, Ford JG: Smoking affects response to inhaled corticosteroids or leukotriene receptor antagonists in asthma. Am J Respir Crit Care Med 2007, 175:783-790.
• [42]Kohlmeier JE, Woodland DL: Immunity to respiratory viruses. Annu Rev Immunol 2009, 27:61-82.
• [43]Khaitov MR, Laza-Stanca V, Edwards MR, Walton RP, Rohde G, Contoli M, Papi A, Stanciu LA, Kotenko SV, Johnston SL: Respiratory virus induction of alpha-, beta- and lambda-interferons in bronchial epithelial cells and peripheral blood mononuclear cells. Allergy 2009, 64:375-386.
• [44]Contoli M, Message SD, Laza-Stanca V, Edwards MR, Wark PA, Bartlett NW, Kebadze T, Mallia P, Stanciu LA, Parker HL: Role of deficient type III interferon-lambda production in asthma exacerbations. Nat Med 2006, 12:1023-1026.
• [45]Cakebread JA, Xu Y, Grainge C, Kehagia V, Howarth PH, Holgate ST, Davies DE: Exogenous IFN-beta has antiviral and anti-inflammatory properties in primary bronchial epithelial cells from asthmatic subjects exposed to rhinovirus. J Allergy Clin Immunol 2011, 127:1148-1154. e1149
• [46]Laza-Stanca V, Stanciu LA, Message SD, Edwards MR, Gern JE, Johnston SL: Rhinovirus replication in human macrophages induces NF-kappaB-dependent tumor necrosis factor alpha production. J Virol 2006, 80:8248-8258.
• [47]Wang J, Oberley-Deegan R, Wang S, Nikrad M, Funk CJ, Hartshorn KL, Mason RJ: Differentiated human alveolar type II cells secrete antiviral IL-29 (IFN-lambda 1) in response to influenza A infection. J Immunol 2009, 182:1296-1304.
• [48]Siren J, Pirhonen J, Julkunen I, Matikainen S: IFN-alpha regulates TLR-dependent gene expression of IFN-alpha, IFN-beta, IL-28, and IL-29. J Immunol 2005, 174:1932-1937.
• [49]Sheppard P, Kindsvogel W, Xu W, Henderson K, Schlutsmeyer S, Whitmore TE, Kuestner R, Garrigues U, Birks C, Roraback J: IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat Immunol 2003, 4:63-68.
• [50]Kim HM, Lee YW, Lee KJ, Kim HS, Cho SW, Van Rooijen N, Guan Y, Seo SH: Alveolar macrophages are indispensable for controlling influenza viruses in lungs of pigs. J Virol 2008, 82:4265-4274.
• [51]Kumagai Y, Takeuchi O, Kato H, Kumar H, Matsui K, Morii E, Aozasa K, Kawai T, Akira S: Alveolar macrophages are the primary interferon-alpha producer in pulmonary infection with RNA viruses. Immunity 2007, 27:240-252.
• [52]Pribul PK, Harker J, Wang B, Wang H, Tregoning JS, Schwarze J, Openshaw PJ: Alveolar macrophages are a major determinant of early responses to viral lung infection but do not influence subsequent disease development. J Virol 2008, 82:4441-4448.
• [53]Woodruff PG, Koth LL, Yang YH, Rodriguez MW, Favoreto S, Dolganov GM, Paquet AC, Erle DJ: A distinctive alveolar macrophage activation state induced by cigarette smoking. Am J Respir Crit Care Med 2005, 172:1383-1392.
• [54]Shaykhiev R, Krause A, Salit J, Strulovici-Barel Y, Harvey BG, O’Connor TP, Crystal RG: Smoking-dependent reprogramming of alveolar macrophage polarization: implication for pathogenesis of chronic obstructive pulmonary disease. J Immunol 2009, 183:2867-2883.
• [55]Hunninghake GW, Gadek JE, Kawanami O, Ferrans VJ, Crysta l RG: Inflammatory and immune processes in the human lung in health and disease. Evaluation by bronchoalveolar lavage. Am J Pathol 1979, 97:149-206.
• [56]Richards SW, Peterson PK, Verbrugh HA, Nelson RD, Hammerschmidt DE, Hoidal JR: Chemotactic and phagocytic responses of human alveolar macrophages to activated complement components. Infect Immun 1984, 43:775-778.
• [57]Holt PG: Immune and inflammatory function in cigarette smokers. Thorax 1987, 42:241-249.
• [58]Marti-Lliteras P, Regueiro V, Morey P, Hood DW, Saus C, Sauleda J, Agusti AG, Bengoechea JA, Garmendia J: Nontypeable Haemophilus influenzae clearance by alveolar macrophages is impaired by exposure to cigarette smoke. Infect Immun 2009, 77:4232-4242.
• [59]King TE Jr, Savici D, Campbell PA: Phagocytosis and killing of Listeria monocytogenes by alveolar macrophages: smokers versus nonsmokers. J Infect Dis 1988, 158:1309-1316.
• [60]Cosio BG, Tsaprouni L, Ito K, Jazrawi E, Adcock IM, Barnes PJ: Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages. J Exp Med 2004, 200:689-695.
• [61]Cosio MG, Saetta M, Agusti A: Immunologic aspects of chronic obstructive pulmonary disease. N Engl J Med 2009, 360:2445-2454.
• [62]McCrea KA, Ensor JE, Nall K, Bleecker ER, Hasday JD: Altered cytokine regulation in the lungs of cigarette smokers. Am J Respir Crit Care Med 1994, 150:696-703.
• [63]Morrison D, Strieter RM, Donnelly SC, Burdick MD, Kunkel SL, MacNee W: Neutrophil chemokines in bronchoalveolar lavage fluid and leukocyte-conditioned medium from nonsmokers and smokers. Eur Respir J 1998, 12:1067-1072.
• [64]Ohta T, Yamashita N, Maruyama M, Sugiyama E, Kobayashi M: Cigarette smoking decreases interleukin-8 secretion by human alveolar macrophages. Respir Med 1998, 92:922-927.
• [65]Hutchens M, Luker KE, Sottile P, Sonstein J, Lukacs NW, Nunez G, Curtis JL, Luker GD: TLR3 increases disease morbidity and mortality from vaccinia infection. J Immunol 2008, 180:483-491.
• [66]Bunting RA, Duffy KE, Lamb RJ, San Mateo LR, Smalley K, Raymond H, Liu X, Petley T, Fisher J, Beck H: Novel antagonist antibody to TLR3 blocks poly(I:C)-induced inflammation in vivo and in vitro. Cell Immunol 2011, 267:9-16.
• [67]Cavassani KA, Ishii M, Wen H, Schaller MA, Lincoln PM, Lukacs NW, Hogaboam CM, Kunkel SL: TLR3 is an endogenous sensor of tissue necrosis during acute inflammatory events. J Exp Med 2008, 205:2609-2621.
• [68]Henson PM, Tuder RM: Apoptosis in the lung: induction, clearance and detection. Am J Physiol Lung Cell Mol Physiol 2008, 294:L601-L611.
• [69]Hodge S, Hodge G, Brozyna S, Jersmann H, Holmes M, Reynolds PN: Azithromycin increases phagocytosis of apoptotic bronchial epithelial cells by alveolar macrophages. Eur Respir J 2006, 28:486-495.
• [70]Hodge S, Hodge G, Scicchitano R, Reynolds PN, Holmes M: Alveolar macrophages from subjects with chronic obstructive pulmonary disease are deficient in their ability to phagocytose apoptotic airway epithelial cells. Immunol Cell Biol 2003, 81:289-296.
• [71]Richens TR, Linderman DJ, Horstmann SA, Lambert C, Xiao YQ, Keith RL, Boe DM, Morimoto K, Bowler RP, Day BJ: Cigarette smoke impairs clearance of apoptotic cells through oxidant-dependent activation of RhoA. Am J Respir Crit Care Med 2009, 179:1011-1021.
• [72]Vandivier RW, Henson PM, Douglas IS: Burying the dead: the impact of failed apoptotic cell removal (efferocytosis) on chronic inflammatory lung disease. Chest 2006, 129:1673-1682.
• [73]Hodge S, Hodge G, Ahern J, Jersmann H, Holmes M, Reynolds PN: Smoking alters alveolar macrophage recognition and phagocytic ability: implications in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2007, 37:748-755.
• [74]Drömann D, Goldmann T, Tiedje T, Zabel P, Dalhoff K, Schaaf B: Toll-like receptor 2 expression is decreased on alveolar macrophages in cigarette smokers and COPD patients. Respir Res 2005, 6:68. BioMed Central Full Text
• [75]Doyle I, Ratcliffe M, Walding A, Vanden Bon E, Dymond M, Tomlinson W, Tilley D, Shelton P, Dougall I: Differential gene expression analysis in human monocyte-derived macrophages: impact of cigarette smoke on host defence. Mol Immunol 2010, 47:1058-1065.
• [76]Gaschler GJ, Zavitz CC, Bauer CM, Skrtic M, Lindahl M, Robbins CS, Chen B, Stampfli MR: Cigarette smoke exposure attenuates cytokine production by mouse alveolar macrophages. Am J Respir Cell Mol Biol 2008, 38:218-226.
• [77]Kang MJ, Lee CG, Lee JY, Dela Cruz CS, Chen ZJ, Enelow R, Elias JA: Cigarette smoke selectively enhances viral PAMP- and virus-induced pulmonary innate immune and remodeling responses in mice. J Clin Invest 2008, 118:2771-2784.
• [78]Bonecchi R, Galliera E, Borroni EM, Corsi MM, Locati M, Mantovani A: Chemokines and chemokine receptors: an overview. Front Biosci 2009, 14:540-551.
• [79]Jiang D, Liang J, Campanella GS, Guo R, Yu S, Xie T, Liu N, Jung Y, Homer R, Meltzer EB: Inhibition of pulmonary fibrosis in mice by CXCL10 requires glycosaminoglycan binding and syndecan-4. J Clin Invest 2010, 120:2049-2057.
• [80]Pekarek V, Srinivas S, Eskdale J, Gallagher G: Interferon lambda-1 (IFN-lambda1/IL-29) induces ELR(−) CXC chemokine mRNA in human peripheral blood mononuclear cells, in an IFN-gamma-independent manner. Genes Immun 2007, 8:177-180.
• [81]Korpi-Steiner NL, Bates ME, Lee WM, Hall DJ, Bertics PJ: Human rhinovirus induces robust IP-10 release by monocytic cells, which is independent of viral replication but linked to type I interferon receptor ligation and STAT1 activation. J Leukoc Biol 2006, 80:1364-1374.
• [82]Miller AL, Bowlin TL, Lukacs NW: Respiratory syncytial virus-induced chemokine production: linking viral replication to chemokine production in vitro and in vivo. J Infect Dis 2004, 189:1419-1430.
• [83]Proost P, Vynckier AK, Mahieu F, Put W, Grillet B, Struyf S, Wuyts A, Opdenakker G, Van Damme J: Microbial Toll-like receptor ligands differentially regulate CXCL10/IP-10 expression in fibroblasts and mononuclear leukocytes in synergy with IFN-gamma and provide a mechanism for enhanced synovial chemokine levels in septic arthritis. Eur J Immunol 2003, 33:3146-3153.
• [84]D’Ambrosio D, Mariani M, Panina-Bordignon P, Sinigaglia F: Chemokines and their receptors guiding T lymphocyte recruitment in lung inflammation. Am J Respir Crit Care Med 2001, 164:1266-1275.
• [85]Kohlmeier JE, Cookenham T, Miller SC, Roberts AD, Christensen JP, Thomsen AR, Woodland DL: CXCR3 directs antigen-specific effector CD4+ T cell migration to the lung during parainfluenza virus infection. J Immunol 2009, 183:4378-4384.
• [86]Costa C, Rufino R, Traves SL, Lapa ESJR, Barnes PJ, Donnelly LE: CXCR3 and CCR5 chemokines in induced sputum from patients with COPD. Chest 2008, 133:26-33.
• [87]Han MK, Postma D, Mannino DM, Giardino ND, Buist S, Curtis JL, Martinez FJ: Gender and chronic obstructive pulmonary disease: why it matters. Am J Respir Crit Care Med 2007, 176:1179-1184.
• [88]Antonelli A, Rotondi M, Fallahi P, Ferrari SM, Paolicchi A, Romagnani P, Serio M, Ferrannini E: Increase of CXC chemokine CXCL10 and CC chemokine CCL2 serum levels in normal ageing. Cytokine 2006, 34:32-38.
• [89]Antonelli A, Rotondi M, Fallahi P, Romagnani P, Ferrari SM, Ferrannini E, Serio M: Age-dependent changes in CXC chemokine ligand 10 serum levels in euthyroid subjects. J Interferon Cytokine Res 2005, 25:547-552.