Vplyv vitamínu D na expresiu mRNA cytokínov u IBD

Autori: Lešková Z., Krajčovičová A., Šoltýs K., Stuchlík S., Šturdík I., Koller T., Huorka M., Hlavatý T.

Pracovisko: V. interná klinika Lekárskej fakulty Univerzity Komenského a Univerzitnej nemocnice Bratislava

Abstrakt: 

Background The aetiology of Crohn’s disease (CD) and ulcerative colitis (UC)  is not known.  Recent  data suggest that vitamin D (VD) plays an important role in IBD. Pathways  that are influenced by VD in IBD are poorly understood.

Aim  The aim of this study was to analyse the influence of 25(OH)VD serum concentration on the expression of mRNA proinflammatory cytokines (IL-6,IL-23, TNFα, CCR1 ), regulatory cytokines (IL-10,TLR2,CCR9, CD 207) and transcription factor Fox3P in colonic mucosal samples from IBD patients.

Methods  We performed a cross-sectional study. The cohort consisted of 87 IBD patients (47 CD and 40 UC)  followed at the IBD centre of University Hospital Bratislava-Ružinov. We performed colonoscopy in  each patient and took biopsies from inflammed and if applicable also from non-inflammed mucosa from sigma (CD, UC) and terminal ileum (CD). Serum concentration of 25(OH)VD was assessed in each patient at the time of colonoscopy. mRNA was extracted  from mucosal  biopsy samples for each cytokine and isolated  by RLT buffer. mRNA was reversely transcribed. We  normalized expression of the target genes to the expression of the house-keeping gene (GAPDH).  Then we analysed the correlation between serum concentration 25(OH)VD and the expression of mRNA of inflammatory cytokines from biopsies samples. 

Results In CD we observed a positive correlation of serum concentration 25(OH)VD and mRNA expressions levels of TNFα (r2=0.41, p=0.04), IL-6(r2=0.45, p=0.02), IL-10(r2=0.44, p=0.03), IL-23( r2=0.55, p=0.02), TLR 2( r2=0.04, p=0.04) in inflammed mucosa of terminal ileum. A positive correlation was also observed with  CCR5( r2=0.042, p=0.01) and CCR1( r2=0.33, p=0.03) in non-inflammed mucosa from sigma. We also found a positive correlation between 25(OH)VD and IL-23(r2=0.45, p=0.01), TLR4(r2=0.42, p=0.02), CD 207(r2=0.42, p=0.02), CCR1 (r2=0.52, p=0.002), CCR5 (r2=0.51 p= 0.003) and CD 206(r2=0.43, p=0.01) in non-inflammed  mucosa of sigma in UC.

Conclusion According to our results, VD significantly correlated with the levels of expression of several  inflammatory cytokines including TNFα in colonic mucosa of patients with CD .