Cigarette smoke condensate extracts augment collagen-induced arthritis in mice

doi:10.1016/j.intimp.2010.06.026

International Immunopharmacology

Volume 10, Issue 10, October 2010, Pages 1194-1199

https://doi.org/10.1016/j.intimp.2010.06.026 Get rights and content

Abstract

Although cigarette smoking is a solid environmental risk factor for rheumatoid arthritis (RA) as revealed by epidemiological studies, the scientific basis has not been provided. Proinflammatory cytokines produced by synoviocytes are implicated in the pathogenesis of RA. As cigarette smoke condensate (CSC) is able to up-regulate the production of proinflammatory cytokines from human fibroblast-like synoviocytes, we studied the effect of CSC on induction of arthritis in the mouse model of collagen type II-induced arthritis (CIA). When mainstream CSC or sidestream CSC was administered into DBA/1J mice at the time of immunization with collagen and complete Freund adjuvant, CSC dose-dependently augmented the induction and clinical development of arthritis at both young and older mice. Peritoneal injected mainstream CSC one day before immunization also exhibited the augmenting effect, suggesting the systemic effect of CSC. These results support the etiological role of cigarette smoking in RA.

Research Highlights

► Cigarette smoke condensate administered into mice with the antigen or before immunization augmented the induction and clinical development of arthritis in the mouse model of collagen type II-induced arthritis ►These results support the etiological role of cigarette smoking in RA.

Introduction

Rheumatoid arthritis (RA) is a systemic disease associated with a chronic inflammatory condition in multiple joints. The disease is characterized by proliferation of synoviocytes in inflamed synovia, formation of pannus and production of proinflammatory cytokines and chemokines by synoviocytes [1]. These cytokines contribute to the disease by production of proteases and reactive oxygen intermediates, induction of proliferation of synovial fibroblasts, cartilage degradation, infiltration of inflammatory cells and angiogenesis [2], [3]. Fibroblast-like synoviocytes as well as synovial tissue-infiltrating macrophages are major cells producing the proinflammatory cytokines. Fibroblast-like synoviocytes or transformed cell clones derived from RA patients secrete, constitutively or in response to interleukin-1 (IL-1) or tumor necrosis factor α (TNFα), proinflammatory cytokines, including IL-1α, IL-1β, IL-6 and IL-8 [4], [5]. The critical role of these proinflammatory cytokines in RA has been verified in both RA patients and animal models of arthritis. An improvement of synovial inflammation and decreased joint destruction in RA patients have been reported following treatment with neutralizing anti-TNFα antibody [6], soluble TNF receptor [7], IL-1 receptor antagonist (IL-1ra) [8] or neutralizing anti-IL-6 antibody [9]. However, the etiology and the mechanisms responsible for the cytokine induction and subsequent development of arthritis remain unknown.

Epidemiological studies indicate an association of cigarette smoking with disease outcome in patients with early inflammatory polyarthritis [10], the increase of rheumatoid factor and nodule formation in patients with RA [11], and a strong association between heavy cigarette smoking and RA, particularly in patients without a family history of RA [12]. Especially the risk of smoking for the disease is quite high in individuals, either men or women, with shared epitope (SE) in HLA-DRB1 [13]. In addition, maternal smoking in pregnancy is a determinable factor of infant rheumatoid arthritis and other inflammatory polyarthritis [14]. However, the scientific basis supporting the epidemiological studies has not been provided.

Polycyclic aromatic hydrocarbons (PAHs) such as 3-methylcholanthrene (3-MC), benzo[a]pyrene (B[a]P) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) are much contained in tobacco smoke. We have previously reported that 3-MC, B[a]P and TCDD up-regulated IL-1β mRNA in RA patient-derived SV40 T antigen-transformed human fibroblast-like synoviocyte line MH7A [15], which has similar characteristics as parental synoviocytes [16], [17]. We also reported that cigarette smoke condensate (CSC), either mainstream or sidestream, also induced IL-1α, IL-1β, IL-6 and IL-8 at both mRNA and protein levels in the cells [18]. As proinflammatory cytokines produced by synovial cells are critical for RA, in this study we determined the effects of CSC on induction and clinical development of arthritis in the mouse model of collagen type II-induced arthritis (CIA), an experimental model of human chronic rheumatoid arthritis.

Section snippets

Reagents

Polymyxin B was purchased from SIGMA-ALDRICH Co. (St. Louis, MO, USA). Bovine type II collagen was from KOKEN Co. Ltd. (Tokyo, Japan). Incomplete Freund adjuvant (ICFA) and Mycobacterium butyricum were from BD (Tokyo, Japan). Endotoxin test kit, Endospecy ES-24S Kit was from SEIKAGAKU BIOBUSINESS CORPORATION (Tokyo, Japan). Detection limit was 0.001 EU/ml, where one EU indicates 0.1 ng/ml of Escherichia coli 055:B5-derived endotoxin.

Preparation of cigarette smoke condensate (CSC)

CSC was prepared as described previously [19]. A common American

Mainstream CSC augments induction and clinical development of arthritis in older mouse

In order to examine the effect of CSC on collagen-induced arthritis, mice were immunized with antigen emulsified with ICFA or CFA with or without mainstream CSC (200 μg per mouse) on day 0, boosted with the antigen alone on day 21, and then the development of arthritis was measured. Male mice aged 27 weeks were used for the experiment because male and older mice are prone to develop arthritis as compared to female and young mice. As shown in Fig. 1A, none of the mice immunized with antigen in

Discussion

In this study we showed for the first time that mainstream CSC or sidestream CSC augmented the induction and clinical development of arthritis in collagen-induced arthritis. In this study we used DBA1J male mice for the experiment because male and older mice are prone to develop arthritis as compared to female and young mice. First, mainstream CSC appeared to augment the induction and severity of arthritis in older mice. In human onset of RA is most frequent in 40 to 50 years. However, younger

Acknowledgments

We gratefully acknowledge the invaluable aid of Drs. Yuka Itoh, Saotomo Itoh, Ryosuke Yokoyama, Kunihiko Akita, Toshiaki Makino, Hajime Mizukami and Satoshi Kanazawa of Nagoya City University. This work was supported in part by Grant-in-Aids for Scientific Research (C) from Japan Society for the Promotion of Science, Grant-in-Aid for Research in Nagoya City University and a grant from the Smoking Research Foundation.

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Cigarette smoke condensate extracts augment collagen-induced arthritis in mice

Abstract

Research Highlights

Introduction

Section snippets

Reagents

Preparation of cigarette smoke condensate (CSC)

Mainstream CSC augments induction and clinical development of arthritis in older mouse

Discussion

Acknowledgments

Cytokine

Rheum Dis Clin North Am

J Biol Chem

Food Chem Toxicol

Toxicol Lett

Lancet

Mononuclear phagocytes and rheumatoid synovitis. Mastermind or workhorse in arthritis?

Arthritis Rheum

Inhibition of the production and effects of interleukin-1 and tumor necrosis factor alpha in rheumatoid arthritis

Arthritis Rheum

Chemokines in rheumatoid arthritis

Springer Semin Immunopathol

Interleukin-1 and tumour necrosis factor mRNA expression in rheumatoid arthritis: prolonged production of IL-1 alpha

Clin Exp Immunol

Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group. Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group

N Engl J Med

Anakinra: review of recombinant human interleukin-1 receptor antagonist in the treatment of rheumatoid arthritis

Clin Ther

Therapeutic benefit of blocking interleukin-6 activity with an anti-interleukin-6 receptor monoclonal antibody in rheumatoid arthritis: a randomized, double-blind, placebo-controlled, dose-escalation trial

Arthritis Rheum

The association of cigarette smoking with disease outcome in patients with early inflammatory polyarthritis

Arthritis Rheum

Smoking, lung function, and rheumatoid factors

Ann Rheum Dis