Role of Interleukin-17 in Acute Pancreatitis

Abstract

Acute pancreatitis (AP) is a leading cause of death and is commonly accompanied by systemic manifestations that are generally associated with a poor prognosis. Many cytokines contribute to pancreatic tissue damage and cause systemic injury. Interleukin-17 (IL-17) is a cytokine that may play a vital role in AP. Specifically, IL-17 has important effects on the immune response and causes interactions between different inflammatory mediators in the AP-related microenvironment. In this literature review, we will discuss the existing academic understanding of IL-17 and the impacts of IL-17 in different cells (especially in acinar cells and immune system cells) in AP pathogenesis. The clinical significance and potential mechanisms of IL-17 on AP deterioration are emphasized. The evidence suggests that inhibiting the IL-17 cytokine family could alleviate the pathogenic process of AP, and we highlight therapeutic strategies that directly or indirectly target IL-17 cytokines in acute pancreatitis.

WITHDRAWN: Gut microbiota aggravates neutrophil extracellular traps-induced pancreatic injury in hypertriglyceridemic pancreatitis

“…In addition, neutrophil extracellular trap formation pathway was activated in FMT-HTGP mice (Figure 3I), gene signatures (Padi4, Cd177, Clec7a and Mpo) that related to neutrophil extracellular trap formation were up-regulated (Figure 3H) 18 . Those pathways (IL-17, NF-kB and NOD-like receptor signaling pathways) that can drive NETs formation, were also activated in FMT-HTGP mice (Figure S3F) [19][20][21] .…”

Xanthohumol alleviates oxidative stress and impaired autophagy in experimental severe acute pancreatitis through inhibition of AKT/mTOR

“…IL-10, a cytokine that combats inflammation, reduces inflammation by inhibiting cytokine production like TNF-α ( Sziksz et al, 2015 ; Palathingal Bava et al, 2022 ). Studies have confirmed that the administration of therapeutic drugs would protect SAP by attenuating the pro-inflammatory cytokine and recovering the IL-10 level, which is in line with our study ( Wang et al, 2011 ; Silva-Vaz et al, 2020 ; Li et al, 2021 ; Palathingal Bava et al, 2022 ). Further, when inhibiting autophagy, the anti-inflammatory effect of Xn was partially lost.…”

“…IL-6, as an early biomarker of severe organ failure and death, produces broad pro-inflammatory effects and leads to tissue damage ( Zhang et al, 2013 ). IL-17 affects immune responses and interacts with inflammatory mediators in SAP-related microenvironments ( Li et al, 2021 ). IL-10, a cytokine that combats inflammation, reduces inflammation by inhibiting cytokine production like TNF-α ( Sziksz et al, 2015 ; Palathingal Bava et al, 2022 ).…”

“…Serum interleukin-17 (IL-17) concentrations in SAP patients correlate with disease severity, making it a novel indicator with predictive value ( Dai et al, 2015 ; Li et al, 2021 ). Interestingly, IL-17 affects autophagy differently depending on the cell type.…”

USP25 Deficiency Exacerbates Acute Pancreatitis via Up-Regulating TBK1–NF-κB Signaling in Macrophages

“…Zhong et al 32 identified USP25 as a negative regulator of interleukin (IL)17-mediated signaling and showed that Usp25 -/- mice show a greater sensitivity to IL17-dependent inflammation and autoimmunity. Because IL17 has been shown to participate in AP pathogenesis, 29 , 33 we wondered if the anti-inflammatory effects of USP25 were mediated through the modulation of the IL17 pathway. Surprisingly, when compared with the WT BMDMs, transcript levels of Il17a and downstream Ccl7 , Ccl20 , Cxcl5 , Tnf , and Cxcl1 were not increased significantly in ACS- or IL17A-exposed Usp25 -/- BMDMs ( Figure 11 A and B ).…”