Molecular aspects of rheumatoid arthritis: role of environmental factors

Kobayashi, Shū; Momohara, Shigeki; Kamatani, Naoyuki; Okamoto, Hiroshi

doi:10.1111/j.1742-4658.2008.06581.x

Cited by 44 publications

(40 citation statements)

References 46 publications

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“…[51][52][53][54][55][56] In some articles, the case is made for causation by a single organism, while in others multiple organisms are argued to be etiologic for RA [55][56][57][58] (see Table 1). 53,54,59 As developed below, we favor the multiple organism hypothesis, although in a rather different …”

Section: Studies Targeting the Etiology Of Rheumatoid Arthritis: Infementioning

confidence: 99%

“…67 Among these microbes possibly associated with induction of RA, EBV and P. mirabilis have been extensively studied and present perhaps the most consistent data in support of infection as a causative factor in RA. 59,67 Elevated antibodies specifically targeting EBV and P. mirabilis have been identified in RA samples. 58,65 Moreover, both of these infectious agents contain antigen proteins/peptides that share a similar molecular structure to that of host tissue peptides, and which therefore can perpetuate inappropriate immune reactions to self.…”

Section: Dovepressmentioning

confidence: 99%

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Rheumatoid arthritis: Disease or syndrome?

Stanich

Carter

Whittum-Hudson

et al. 2009

OARRR

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Rheumatoid arthritis (RA) has been described in the medical literature for over two hundred years, but its etiology remains unknown. RA displays phenotypic heterogeneity, and it is a relatively prevalent clinical entity: it affects approximately 1% of the population, resulting in enormous pathologic sequelae. Earlier studies targeting the cause(s) of RA suggested potential infectious involvement, whereas more recent reports have focused on a genetic origin of the disease. However, neither infection nor genetics, nor any other single factor is currently accepted as causative of RA. In this article we review studies relating to the etiology of RA, and those of several related matters, and we conclude that the literature indeed does provide insight into the causes underlying the initiation of RA pathogenesis. Briefly, given the remarkable phenotypic variation of RA, especially in its early stages, as well as a number of other characteristics of the condition, we contend that RA is not a discrete clinical entity with a single etiological source. Rather, we argue that it represents a common clinical endpoint for various starting points, each of which is largely guided by as yet poorly understood aspects of the genetic background of the affected individual. Adoption of this alternative view of the origin of RA will have significant consequences for future research and for development of new therapeutic interventions for this burdensome condition.

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Section: Studies Targeting the Etiology Of Rheumatoid Arthritis: Infementioning

confidence: 99%

Section: Dovepressmentioning

confidence: 99%

Rheumatoid arthritis: Disease or syndrome?

Stanich

Carter

Whittum-Hudson

et al. 2009

OARRR

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“…These data suggest that TNF-α activates AhR expression in RA synovial tissue, and thus cigarette smoking and exposure to TCDD enhances the RA inflammatory processes. Thus, TCDD exposure, such as during smoking, appears to exacerbate RA pathogenesis [16]. As tobacco smoke is a rich source of planar polycyclic aromatic hydrocarbons, many of which are AhR agonists (e.g.…”

Section: Commentarymentioning

confidence: 99%

Smoking and the Microbiome in the Pathogenesis of Rheumatoid Arthritis

Okamoto¹

2014

Rheumatol Curr Res

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“…Cigarette smoking is the most common environmental trigger and predicts both the susceptibility and severity of disease. Other environmental triggers that predispose individuals to RA are exposure to infectious agents and an imbalance in steroid hormones (9).…”

Section: Rheumatoid Arthritismentioning

confidence: 99%

Thymosin β4 in rheumatoid arthritis: Friend or foe

Kim

Yang

2017

Biomedical Reports

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Abstract. Rheumatoid arthritis (RA) has characteristic pannus tissues, which show tumor-like growth of the synovium through chronic joint inflammation. The synovium is highly penetrated by various immune cells, and the synovial lining becomes hyperplastic due to increased numbers of macrophage-like and fibroblast-like synoviocytes. Thus, a resultant hypoxic condition stimulates the expression of inflammation-related genes in various cells, in particular, vascular endothelial growth factor. Thymosin β4 (Tβ4), a 5-kDa protein, is known to play a significant role in various biological activities, such as actin sequestering, cell motility, migration, inflammation, and damage repair. Recent studies have provided evidence that Tβ4 may have a role in RA pathogenesis. The Tβ4 level has been shown to increase significantly in the joint fluid and serum of RA patients. However, whether Tβ4 stimulates or inhibits activation of RA immune responses remains to be determined. In the present study, we discuss the logical and clinical justifications for Tβ4 as a potential target for RA therapeutics. IntroductionCytokines control an extensive range of inflammatory progressions that are associated with the pathogenesis of rheumatoid arthritis (RA). In arthritic joints, pro-inflammatory activities lead to the induction of autoimmunity, chronic inflammation, and, ultimately, joint damage (1). A better understanding of these pathogenic mechanisms has enabled the development of therapeutic agents to inhibit cytokine actions, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1, and IL-6, which have greatly contributed to the management of RA patients (2,3). Biological therapies have contributed innovative improvements to RA treatment (4). However, despite these improvements, 30-50% of RA patients who are non-responders to disease-modifying antirheumatic drugs (DMARDs) fail to respond to treatment with biologic agents (5). Furthermore, radiographic joint damage can proceed even when clinical disease reduction is achieved by biologic agents (6).These results indicate that the inhibition of cytokine networks may not be satisfactory to suppress RA progression. Thus, there is a need for new therapeutic agents to target new molecules, which encouraged us to redirect our efforts to screen other therapeutic targets from joint synovial fluids of RA patients. Recently, we observed that the level of thymosin β4 (Tβ4), which has many biological roles, was significantly increased in the serum and joint fluids of RA patients (7,8). This review aims to discuss the current understanding of the potential role of Tβ4 in RA pathogenesis while addressing current knowledge regarding the association between Tβ4 and arthritic joints for RA management. Rheumatoid arthritisRA is an autoimmune inflammatory disease whose pathogenic mechanisms remain elusive. RA pathogenesis is attributed to a complex interaction between genetic and environmental factors (7). The class II major histocompatibility complex molecules HLA-DR1 and HLA-DR4 are regarded as major...

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Molecular aspects of rheumatoid arthritis: role of environmental factors

Cited by 44 publications

References 46 publications

Rheumatoid arthritis: Disease or syndrome?

Rheumatoid arthritis: Disease or syndrome?

Smoking and the Microbiome in the Pathogenesis of Rheumatoid Arthritis

Thymosin β4 in rheumatoid arthritis: Friend or foe

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