Low levels of pannexin‐1 in Behçet’s syndrome

Abstract

Objective Behçet's syndrome (BS) is a chronic, multisystemic and inflammatory syndrome. In our study, we aimed to compare the initiator, effector and inflammatory caspases and pannexin channel protein, which is thought to have an activity in inflammation, in the inflammatory process of BS, with healthy subjects, to investigate their level in patients and their relationship with the clinical findings. Method Forty‐six patients who were under follow‐up for BS in the Sivas Cumhuriyet University Medical Faculty Department of Internal Diseases, Rheumatology Unit, between January 2017 and June 2017 and 44 healthy controls (HC) who did not have any rheumatic, systemic or metabolic diseases, were enrolled in this study. Results The mean serum pannexin‐1 level was 6.36 (4.21‐527.2) pg/mL in the BS group and 255.8 (5.38‐2000) pg/mL in the HC group. Serum pannexin‐1 levels were statistically significantly lower in the BS group (P < 0.0001). The measured mean serum caspase‐3 level was 12.04 (11.25‐43.69) pg/mL in the group with BS and 12.1 (11.19‐484.3) pg/mL in the HC group (P = 0.143), mean serum caspase‐9 level was 22 (5.14‐29.33) pg/mL in the BS group and 22.01 (11.23‐850) pg/mL in the HC group (P = 0.593), mean serum caspase‐14 level was 6 (5.2‐8.21) pg/mL in the BS group and 6.15 (5.7‐353) pg/mL in the HC group (P = 0.053). Conclusion Comparison of serum caspase‐3, caspase‐9 and caspase‐14 levels in subjects with BS and in the HC group did not reveal any statistically significant differences. On the other hand, serum pannexin‐1 levels were statistically significantly lower in the BS group.

Pep27 Mutant Immunization Inhibits Caspase-14 Expression to Alleviate Inflammatory Bowel Disease via Treg Upregulation

“…We found significant upregulation of the caspase-14 as one of the contributing factors in the pathogenesis of IBD. In support of this, several inflammatory and oxidative stress models suggest collateral induction of caspase-3 and caspase-14 [43,44], thereby increasing cytokines level [30]. In the DIC model, caspase-3 is a well-defined apoptotic marker [45].…”

“…∆pep27 upregulated Tregs and increased the levels of anti-inflammatory transcripts (IL-10 in particular) in the VEET and VIVIT groups, suggesting that ∆pep27 upregulated the Treg-dependent blockade of NFAT that can be an alternate therapeutic target in IBD [20]. Moreover, caspase-14 is considered as an inflammatory and apoptotic marker for cytokine activation in the chronic inflammatory Behcet's disease [30]. Once caspase-14 has been biochemically characterized, it could be considered as an alternate IBD therapeutic target.…”

“…considered as an inflammatory and apoptotic marker for cyto chronic inflammatory Behcet's disease [30]. Once caspase-14 h characterized, it could be considered as an alternate IBD therapeu…”

“…An insight into the system biology analysis configures the protective role of ∆pep27 to mitigate the dysregulated immune response and aberrant cytokines production via antioxidant genes induction and regulating signaling pathways in colon (Figure 2A). Transcriptome analyses showed that the caspase-14 gene, a member of the caspase-1 family responsible for cytokine activation and apoptosis in keratinocytes [29,30], was significantly upregulated but not defined in IBD (Figure 2A). ∆pep27 dose-dependent activity suggested that three repeats of ∆pep27 immunization significantly attenuated DIC-induced proinflammatory and inflammatory mediators comprising TNF-α, IL-17A, and caspase-14 at mRNA and protein levels (Figures 1J,K…”