Etiological role of cigarette smoking in rheumatoid arthritis: Nasal exposure to cigarette smoke condensate extracts augments the development of collagen-induced arthritis in mice

2011 ◽  
Vol 404 (4) ◽  
pp. 1088-1092 ◽  
Author(s):  
Shosuke Okamoto ◽  
Miki Adachi ◽  
Satomi Chujo ◽  
Kyohei Yamada ◽  
Kunihiko Akita ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Cigarette Smoke Condensate ◽  
Collagen Induced Arthritis ◽  
Etiological Role

scholarly journals Inhibition of miR‐155 Attenuates Detrimental Vascular Effects of Tobacco Cigarette Smoking

2020 ◽  
Vol 9 (24) ◽  
Author(s):  
Giacomo Frati ◽  
Maurizio Forte ◽  
Flavio di Nonno ◽  
Antonella Bordin ◽  
Isotta Chimenti ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Cells ◽  
Cigarette Smoking ◽  
Cigarette Smoke ◽  
Healthy Subjects ◽  
Cigarette Smoke Condensate ◽  
Human Endothelial Cells ◽  
Vascular Effects ◽  
Tobacco Cigarette

Background The role of microRNAs dysregulation in tobacco cigarette smoking–induced vascular damage still needs to be clarified. We assessed the acute effects of tobacco cigarette smoking on endothelial cell‐related circulating microRNAs in healthy subjects. In addition, we investigated the potential role of microRNAs in smoking‐dependent endothelial cell damage. Methods and Results A panel of endothelial‐related microRNAs was quantified in healthy subjects before and after smoking 1 tobacco cigarette. Serum levels of miR‐155 were found to be significantly increased shortly after smoking. We also observed a progressive and significant miR‐155 accumulation in culture media of human endothelial cells after 30 minutes and up to 4 hours of cigarette smoke condensate treatment in vitro without evidence of cell death, indicating that miR‐155 can be released by endothelial cells in response to smoking stress. Cigarette smoke condensate appeared to enhance oxidative stress and impair cell survival, angiogenesis, and NO metabolism in human endothelial cells. Notably, these effects were abrogated by miR‐155 inhibition. We also observed that miR‐155 inhibition rescued the deleterious effects of cigarette smoke condensate on endothelial‐mediated vascular relaxation and oxidative stress in isolated mouse mesenteric arteries. Finally, we found that exogenous miR‐155 overexpression mimics the effects of smoking stress by inducing the upregulation of inflammatory markers, impairing angiogenesis and reducing cell survival. These deleterious effects were associated with downregulation of vascular endothelial growth factor and endothelial NO synthetase. Conclusions Our results suggest that miR‐155 dysregulation may contribute to the deleterious vascular effects of tobacco smoking.

scholarly journals Secreted KIAA1199 promotes the progression of rheumatoid arthritis by mediating hyaluronic acid degradation in an ANXA1-dependent manner

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Wei Zhang ◽  
Guoyu Yin ◽  
Heping Zhao ◽  
Hanzhi Ling ◽  
Zhen Xie ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Hyaluronic Acid ◽  
Dependent Manner ◽  
Collagen Induced Arthritis ◽  
Intracellular Degradation ◽  
Main Pathway ◽  
First Time

AbstractIn inflamed joints, enhanced hyaluronic acid (HA) degradation is closely related to the pathogenesis of rheumatoid arthritis (RA). KIAA1199 has been identified as a hyaladherin that mediates the intracellular degradation of HA, but its extracellular function remains unclear. In this study, we found that the serum and synovial levels of secreted KIAA1199 (sKIAA1199) and low-molecular-weight HA (LMW-HA, MW < 100 kDa) in RA patients were significantly increased, and the positive correlation between them was shown for the first time. Of note, treatment with anti-KIAA1199 mAb effectively alleviated the severity of arthritis and reduced serum LMW-HA levels and cytokine secretion in collagen-induced arthritis (CIA) mice. In vitro, sKIAA1199 was shown to mediate exogenous HA degradation by attaching to the cell membrane of RA fibroblast-like synoviosytes (RA FLS). Furthermore, the HA-degrading activity of sKIAA1199 depended largely on its adhesion to the membrane, which was achieved by its G8 domain binding to ANXA1. In vivo, kiaa1199-KO mice exhibited greater resistance to collagen-induced arthritis. Interestingly, this resistance could be partially reversed by intra-articular injection of vectors encoding full-length KIAA1199 instead of G8-deleted KIAA119 mutant, which further confirmed the indispensable role of G8 domain in KIAA1199 involvement in RA pathological processes. Mechanically, the activation of NF-κB by interleukin-6 (IL-6) through PI3K/Akt signaling is suggested to be the main pathway to induce KIAA1199 expression in RA FLS. In conclusion, our study supported the contribution of sKIAA1199 to RA pathogenesis, providing a new therapeutic target for RA by blocking sKIAA1199-mediated HA degradation.

scholarly journals Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis

2006 ◽  
Vol 203 (2) ◽  
pp. 325-335 ◽  
Author(s):  
Tetsuya Honda ◽  
Eri Segi-Nishida ◽  
Yoshiki Miyachi ◽  
Shuh Narumiya
Keyword(s):  
Rheumatoid Arthritis ◽  
Synovial Fluid ◽  
Joint Inflammation ◽  
Synovial Fibroblasts ◽  
The Other ◽  
Receptor Subtype ◽  
Significant Suppression ◽  
Wild Type ◽  
Collagen Induced Arthritis

Prostaglandin (PG)I2 (prostacyclin [PGI]) and PGE2 are abundantly present in the synovial fluid of rheumatoid arthritis (RA) patients. Although the role of PGE2 in RA has been well studied, how much PGI2 contributes to RA is little known. To examine this issue, we backcrossed mice lacking the PGI receptor (IP) to the DBA/1J strain and subjected them to collagen-induced arthritis (CIA). IP-deficient (IP−/−) mice exhibited significant reduction in arthritic scores compared with wild-type (WT) mice, despite anti-collagen antibody production and complement activation similar to WT mice. IP−/− mice also showed significant reduction in contents of proinflammatory cytokines, such as interleukin (IL)-6 in arthritic paws. Consistently, the addition of an IP agonist to cultured synovial fibroblasts significantly enhanced IL-6 production and induced expression of other arthritis-related genes. On the other hand, loss or inhibition of each PGE receptor subtype alone did not affect elicitation of inflammation in CIA. However, a partial but significant suppression of CIA was achieved by the combined inhibition of EP2 and EP4. Our results show significant roles of both PGI2-IP and PGE2-EP2/EP4 signaling in the development of CIA, and suggest that inhibition of PGE2 synthesis alone may not be sufficient for suppression of RA symptoms.

Cigarette smoke condensate extracts induce proinflammatory cytokines from synovial cells and exacerbate collagen-induced arthritis in mice

Cytokine ◽  
2009 ◽  
Vol 48 (1-2) ◽  
pp. 94-95
Author(s):  
Kikuo Onozaki ◽  
Satomi Chujo ◽  
Shosuke Okamoto ◽  
Ryohei Sunahara ◽  
Yuka Itoh ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Proinflammatory Cytokines ◽  
Synovial Cells ◽  
Cigarette Smoke Condensate ◽  
Collagen Induced Arthritis

scholarly journals 5-Hydroxy-2-methylpyridine Isolated from Cigarette Smoke Condensate Aggravates Collagen-Induced Arthritis in Mice

2018 ◽  
Vol 41 (6) ◽  
pp. 877-884
Author(s):  
Masafumi Takeno ◽  
Shinya Kitagawa ◽  
Junpei Yamanaka ◽  
Mayumi Teramoto ◽  
Haruka Tomita ◽  
...  
Keyword(s):  
Cigarette Smoke ◽  
Cigarette Smoke Condensate ◽  
Collagen Induced Arthritis

scholarly journals What Have We Learned about the Pathogenesis of Rheumatoid Arthritis from TNF-Targeted Therapy?

2012 ◽  
Vol 2012 ◽  
pp. 1-15 ◽  
Author(s):  
Richard O. Williams
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Susceptibility ◽  
Therapeutic Effects ◽  
Collagen Induced Arthritis ◽  
Inflammatory Bowel ◽  
Genetic And Environmental Factors ◽  
The Impact ◽  
Anti Inflammatory Cytokine ◽  
Pro Inflammatory Cytokines

Studies of cytokine regulation in rheumatoid arthritis led to the development of TNFα inhibitors which are now used for a number of indications, including rheumatoid arthritis, inflammatory bowel disease, psoriasis, psoriatic arthritis, and ankylosing spondylitis. The widespread use of biologics in the clinic offers unique opportunities for probing disease pathogenesis and this paper provides an overview of rheumatoid arthritis, with a particular emphasis on the impact of anti-TNFα therapy on pathogenetic mechanisms. An overview is also provided on the most commonly used animal models that mimic RA, including adjuvant-induced arthritis, collagen-induced arthritis, TNFα-transgenic mice, and the K/BxN and SKG models. These models have led to significant discoveries relating to the importance of pro-inflammatory cytokines in the pathogenesis of rheumatoid arthritis, resulting from disregulation of the normally finely tuned balance of pro- and anti-inflammatory cytokine signalling. In addition, experimental evidence is discussed suggesting how genetic and environmental factors can contribute to disease susceptibility. The role of effector and regulatory T cells is discussed in the light of the relatively disappointing therapeutic effects of T cell modifying agents such as anti-CD4 antibody and cyclosporin. It is concluded that comprehensive analyses of mechanisms of action of biologics and other drugs entering the clinic will be essential to optimise therapy, with the ultimate aim of providing a cure.

The complex role of the chemokine receptor CCR2 in collagen-induced arthritis: implications for therapeutic targeting of CCR2 in rheumatoid arthritis

2005 ◽  
Vol 83 (9) ◽  
pp. 672-681 ◽  
Author(s):  
Marlon P. Quinones ◽  
Carlos A. Estrada ◽  
Yogeshwar Kalkonde ◽  
Sunil K. Ahuja ◽  
William A. Kuziel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Chemokine Receptor ◽  
Collagen Induced Arthritis ◽  
Therapeutic Targeting ◽  
Chemokine Receptor Ccr2
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