Association of IL-12B Genetic Polymorphism with the Susceptibility and Disease Severity of Ankylosing Spondylitis

Wong, Ruey-Hong; Wei, James Cheng‐Chung; Huang, Chun-Huang; Lee, Hong-Shen; Chiou, Shang-Yan; Lin, Shin-Hua; Cai, Yanwei; Hung, Pei-Hsuan; Wang, Ming-Fuu; Yang, Shun-Fa

doi:10.3899/jrheum.110613

Cited by 51 publications

(37 citation statements)

References 40 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with these studies, the current research also showed a higher number of MMP-3 positive cells in synovial tissues from the disease group compared to the control group, and identified a significantly positive relationship between MMP-3 transcript levels and CRP or BASDAI indices. As a major body inflammatory factor, CRP can reflect the severity of AS while the BASDAI score has been widely used to directly evaluate disease progression (van der Linden et al, 1984;Wong et al, 2012). We suggest that this relationship is due to the fact that MMP-3 directly participates in the degradation of the extracellular matrix, and its elevation can activate multiple MMP factor precursors including MMP-1, -9, and -13 to further accelerate the degradation of joint cartilage matrix, destroy cartilage, and advance the progression of AS Kawamura et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Expression of TNF-α, VEGF, and MMP-3 mRNAs in synovial tissues and their roles in fibroblast-mediated osteogenesis in ankylosing spondylitis

Liu¹,

He²,

Tan³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

ABSTRACT. The aim of this study was to explore the mRNA levels of tumor necrosis factor-α (TNF-α), vessel endothelial growth factor (VEGF), and matrix metalloproteinase-3 (MMP-3) in synovial tissues in ankylosing spondylitis (AS), and to analyze the functions of these proteins in the differentiation of AS synovial tissue fibroblasts into osteoblasts (OB) and osteoclasts. Synovial tissue samples from 22 AS patients and 22 normal individuals were collected. In situ hybridization was utilized to detect TNF-α, VEGF, and MMP-3 transcripts. After counting numbers of positive cells, Spearman analysis was used to determine the correlation between transcriptional levels of the three mRNAs and the AS disease activity index (BASDAI) and the C-response protein (CRP) levels. With the addition of TNF-α, VEGF, or both factors into cultured normal synovial fibroblasts, osteocalcin (bone gla protein, BGP) secretion levels were compared. We found that expression of TNF-α, VEGF, and MMP-3 was identified exclusively in the disease group. mRNA levels were significantly positively (2015) correlated with BASDAI (r = 0.42, 0.38, and 0.47, respectively; P < 0.05) and CRP (r = 0.44, 0.34, and 0.47 respectively; P < 0.05) scores. The secretion level of BGP in normal synovial fibroblasts increased progressively with increasing concentrations of VEGF or TNF-α (P < 0.01 compared to levels before treatment). Furthermore, co-incubation using both VEGF and TNF-α significantly elevated BGP levels compared to the single addition of VEGF or TNF-α (P < 0.01). These results suggest TNF-α, VEGF, and MMP-3 might directly participate in the differentiation of fibroblasts into OBs.

show abstract

Section: Discussionmentioning

confidence: 99%

Expression of TNF-α, VEGF, and MMP-3 mRNAs in synovial tissues and their roles in fibroblast-mediated osteogenesis in ankylosing spondylitis

Liu¹,

He²,

Tan³

et al. 2015

Genet. Mol. Res.

View full text Add to dashboard Cite

show abstract

“…Recent GWAS have pointed out a set of polymorphisms in IL-12B gene that is consistently associated with chronic inflammatory disorders. The rs3212227 (A→C) polymorphism present in the 3'UTR region of IL-12B has been associated with psoriasis 111 , type 1 112 and type 2 diabetes mellitus 113 , multiple sclerosis 114 , ankylosing spondylitis 115 , allergic rhinitis 116 , asthma 117 , and lepromatous leprosy 118 . However, the information regarding the association of CAD with polymorphisms present in the IL-12B gene is scarce.…”

Section: Il-12b Genementioning

confidence: 99%

Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis

Posadas-Sánchez

Vargas‐Alarcón

2018

RIC

View full text Add to dashboard Cite

Atherosclerosis is a chronic, progressive, and multifactorial disease modulated by genetic and environmental factors. In recent years, the paradigm that explained atherosclerosis as resulting from a complex interaction between factors not accessible to medical intervention, and modifiable risk factors has changed. In this paradigm, alterations in lipid metabolism were the pivotal concept of atherosclerosis as a chronic degenerative disease. In the last years, an increasing number of observations have shown that the innate and adaptive immune responses to lipoprotein deposition and oxidation in the arterial wall significantly influence atherosclerosis. Currently, it is well recognized that the pathogenesis of atherosclerosis and its complications involves the inflammatory process, which includes the participation of several cytokines. Besides the classic cytokines involved in this process, the role of the interleukin-12 (IL-12) family has been recently demonstrated. This review describes our current understanding about the role of the family of IL-12 in atherosclerosis considering the participation of the genes that encode these cytokines in the genetic susceptibility to developing this disease.

show abstract

“…Te powiązania dotyczą przekazywania sygnału przez czynnik martwicy nowotworu (tumor necrosis factor -TNF) (loci TNFRSF1A, TRADD i TNFSF15), przekazywania sygnału i wytwarzania interleukiny (IL) 1 (polimorficzne odmiany genów IL-1R2, IL-1Ra, IL-1A, IL-1B, IL-1RN), IL-6 (polimorficzna odmiana genu IL-6 i STAT3) oraz IL-23 [13][14][15][16][17][18][19]. Interleukinę 23 tworzą dwa łańcuchy -swoisty dla niej łańcuch IL-23p19 oraz łańcuch IL-12p40, wykorzystywany także przez IL-12.…”

Section: Geny Spoza Układu Hlaunclassified

“…Interleukinę 23 tworzą dwa łańcuchy -swoisty dla niej łańcuch IL-23p19 oraz łańcuch IL-12p40, wykorzystywany także przez IL-12. Łańcuch IL-12p40 jest kodowany przez gen IL-12B, a genotyp IL-12B A1188C zwiększa 2-krotnie ryzyko rozwoju ZZSK i koreluje z klinicznie cięższym przebiegiem choroby [17]. Z ZZSK jest powiązanych również kilka polimorficznych odmian genu kodującego receptor dla IL-23 (IL-23R), przy czym warianty o obniżonej reaktywności na IL-23 są genami protekcyjnymi, a inne genami ryzyka [18,19].…”

Section: Geny Spoza Układu Hlaunclassified

New aspects of spondyloarthritis pathogenesis. Part I. Genetic factors and role of HLA-B27 molecules

Kontny¹

2014

Reumatologia

View full text Add to dashboard Cite

Badania z ostatnich lat weryfikują zrozumienie patogenezy spondyloartropatii zapalnych (SpA). Wskazują one, że tradycyjne podtypy tej choroby mają wspólny komponent patogenezy. Składają się na niego pewne wspólne uwarunkowania genetyczne (allele HLA-B27, warianty genów IL-23R, ERAP1, ERAP2), które omówiono w niniejszym artykule. Oprócz tego istnieją podobieństwa dotyczące czynników środowiskowych i mechanizmów immunologicznych, co będzie przedmiotem następnych opracowań. Zmienił się również pogląd na rolę cząsteczek HLA-B27 w patogenezie SpA. Cząsteczki HLA-B27 występują w formie klasycznej i nieklasycznej, jako pojedyncze łańcuchy ciężkie lub ich homodimery. Cząsteczki klasyczne prezentują antygeny własne i obce, inicjując nabytą odpowiedź immunologiczną, natomiast cząsteczki nieklasyczne indukują odpowiedź autozapalną. W artykule omówiono również to zagadnienie.

show abstract

Association of IL-12B Genetic Polymorphism with the Susceptibility and Disease Severity of Ankylosing Spondylitis

Abstract: The IL-12B A1188C genotype was associated with the development and disease severity of AS.

Cited by 51 publications

References 40 publications

Expression of TNF-α, VEGF, and MMP-3 mRNAs in synovial tissues and their roles in fibroblast-mediated osteogenesis in ankylosing spondylitis

Expression of TNF-α, VEGF, and MMP-3 mRNAs in synovial tissues and their roles in fibroblast-mediated osteogenesis in ankylosing spondylitis

Innate Immunity in Coronary Disease. The Role of Interleukin-12 Cytokine Family in Atherosclerosis

New aspects of spondyloarthritis pathogenesis. Part I. Genetic factors and role of HLA-B27 molecules

Contact Info

Product

Resources

About