Joint cytokine quantification in two rodent arthritis models: kinetics of expression, correlation of mRNA and protein levels and response to prednisolone treatment

Rioja, Inma; Bush, K. A.; Buckton, J; Dickson, Marion C.; Life, Paul

doi:10.1111/j.1365-2249.2004.02499.x

Cited by 111 publications

(86 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the rat synovium, levels of IL-1␤ and TNF-␣ protein correlate well with their respective amount of mRNA (55). Therefore, we used quantitative real-time PCR to study the changes in levels of these two cytokines in rats studied for PIA, and determined that IL-1␤ levels were reduced in DA.F344(Cia5), as well as in its subcongenic DA.F344(Cia5a) (and to a lesser degree Cia5d) rats compared with DA rats, suggesting that the genes accounting for these QTLs influence inflammatory processes upstream from this cytokine.…”

Section: Discussionmentioning

confidence: 89%

“…One likely explanation is the timing of the synovial tissue collection. Specifically, we obtained synovial tissues after the completion of the arthritis observation period (day 32), a time point that was beyond the peak of the synovial levels of TNF-␣ in rats (55,56). Interestingly, even at this late stage differences in cytokine expression could still be detected, underscoring the regulatory effect of Cia5a and Cia5d genes during later stages of the disease course.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The Non-MHC Quantitative Trait LocusCia5Contains Three Major Arthritis Genes That Differentially Regulate Disease Severity, Pannus Formation, and Joint Damage in Collagen- and Pristane-Induced Arthritis

Meng

Yarlett

Joe

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

Cia5 is a locus on rat chromosome 10 which regulates the severity of collagen- and pristane-induced arthritis (CIA and PIA). To refine the region toward positional identification, Cia5 subcongenic strains were generated and studied in PIA and CIA. The protective effect of the telomeric locus Cia5a was confirmed in both models. A second arthritis severity locus (Cia5d) was identified within the most centromeric portion of Cia5. DA.F344(Cia5d) rats had a significantly lower median arthritis severity index in PIA, but not in CIA, compared with DA. On histologic analyses DA.F344(Cia5a) and DA.F344(Cia5d) congenics with PIA preserved a nearly normal joint architecture compared with DA, including significant reduction in synovial hyperplasia, pannus, angiogenesis, inflammatory infiltration, bone and cartilage erosions. Cia5 and Cia5a synovial levels of IL-1β mRNA were reduced. Although both DA.F344(Cia5) and DA.F344(Cia5a) rats were protected in CIA, the arthritis scores of DA.F344(Cia5) were significantly higher than those of DA.F344(Cia5a), suggesting the existence of a third locus where F344-derived alleles centromeric from Cia5a contribute to increased arthritis severity. The existence of the third locus was further supported by higher levels of autoantibodies against rat type II collagen in DA.F344(Cia5) congenics compared with DA.F344(Cia5a). Our results determined that Cia5 contains three major arthritis severity regulatory loci regulating central events in the pathogenesis of arthritis, and differentially influencing CIA and PIA. These loci are syntenic to regions on human chromosomes 17q and 5q implicated in the susceptibility to rheumatoid arthritis, suggesting that the identification of these genes will be relevant to human disease.

show abstract

Section: Discussionmentioning

confidence: 89%

Section: Discussionmentioning

confidence: 99%

The Non-MHC Quantitative Trait LocusCia5Contains Three Major Arthritis Genes That Differentially Regulate Disease Severity, Pannus Formation, and Joint Damage in Collagen- and Pristane-Induced Arthritis

Meng

Yarlett

Joe

et al. 2005

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…These differing results may be partly explained by the lack of correlation between tissue mRNA concentrations and protein concentrations in this study. Although some groups have demonstrated a correlation between IL-1b and IL-6 mRNA and protein concentrations in an animal model of inflammatory joint disease, they also failed to show any correlation for TNF-a mRNA and protein concentrations (Rioja et al, 2004). The difficulties of relating mRNA concentrations to protein concentrations has been extensively documented elsewhere, but it is also important to consider that real-time PCR is an exquisitely sensitive technique and that what we are detecting in some patients, although elevated, may have little or no functional significance as it may not be translated into protein.…”

Section: Discussionmentioning

confidence: 97%

Elevated tumour interleukin-1β is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer

et al. 2006

View full text Add to dashboard Cite

Systemic inflammation is associated with adverse prognosis cancer but its aetiology remains unclear. We investigated the expression of proinflammatory cytokines within normal mucosa from healthy controls and tumour tissue in cancer patients and related these levels with markers of systemic inflammation and with the presence of a tumour inflammatory infiltrate. Tissue was collected from 56 patients with gastro-oesophageal cancer and from 12 healthy controls. Tissue cytokine mRNA concentrations were measured by real-time PCR and tissue protein concentrations by cytometric bead array. The degree of chronic inflammatory cell infiltrate was recorded. Serum cytokine and acute phase protein concentrations (including C-reactive protein (CRP)) were measured by enzymelinked immunosorbent assay. Proinflammatory cytokines were significantly overexpressed (interleukin (IL)-1b, IL-6, IL-8 and tumour necrosis factor-a) both at mRNA and protein levels in the cancer specimens compared with mucosa from controls. Interleukin-1b was expressed in greatest (10 -100-fold) concentration and protein levels correlated significantly with systemic inflammation (CRP) (P ¼ 0.05, r ¼ 0.31). A chronic inflammatory infiltrate was observed in 75% of the cancer specimens and was associated with systemic inflammation (CRP: P ¼ 0.01). However, the presence of chronic inflammation per se was not associated with altered cytokine expression within the tumour. Both a chronic inflammatory infiltrate and systemic inflammation (CRP) were associated with reduced survival (P ¼ 0.05 and P ¼ 0.03, respectively). Tumour chronic inflammatory infiltrate and tumour tissue IL-1b overexpression are potential independent factors influencing systemic inflammation in oesophagogastric cancer patients.

show abstract

“…Furthermore, the animals can be monitored for a longer period of time, because the disease is less severe compared with other models of arthritis. Of note, the kinetics of the expression of cytokines such as IL-1␤, IL-6, and TNF␣ suggest that the optimal time point for evaluating the efficacy of treatment is 3 days after intravenous challenge (60).…”

Section: Evaluation Of Therapeutic Targets In Animal Models Of Arthritismentioning

confidence: 99%

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

Bevaart¹,

Vervoordeldonk²,

Tak³

2010

Arthritis & Rheumatism

228

193

View full text Add to dashboard Cite

There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi‐ethnic cohort from the developing nation of Mauritius. Population‐based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h‐PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00‐7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.98–2.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations.

show abstract

Joint cytokine quantification in two rodent arthritis models: kinetics of expression, correlation of mRNA and protein levels and response to prednisolone treatment

Cited by 111 publications

References 29 publications

The Non-MHC Quantitative Trait LocusCia5Contains Three Major Arthritis Genes That Differentially Regulate Disease Severity, Pannus Formation, and Joint Damage in Collagen- and Pristane-Induced Arthritis

The Non-MHC Quantitative Trait LocusCia5Contains Three Major Arthritis Genes That Differentially Regulate Disease Severity, Pannus Formation, and Joint Damage in Collagen- and Pristane-Induced Arthritis

Elevated tumour interleukin-1β is associated with systemic inflammation: a marker of reduced survival in gastro-oesophageal cancer

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

Contact Info

Product

Resources

About