Gαi2 and Gαq Expression Change in Pancreatic Tissues and BN52021 Effects in Rats With Severe Acute Pancreatitis

Xia, Shihai; Hu, Chunxiu; Fang, Jinmiao; Di, Yao; Zhao, Zhenjuan; Liu, Li-rong

doi:10.1097/mpa.0b013e3181661b07

Cited by 6 publications

(3 citation statements)

References 20 publications

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“…The pathogenesis of SAP has not been completely clarified until now [12], and experts have their attention to cytokine network and immune damage, which are the main pathological mechanisms for SAP [9]. It is generally agreed that systemic inflammation triggers pancreatitis by itself involving multiple pathways (inflammatory cellular factors, inflammatory mediators, and vascular active substances), starts the SIRS, and results in an exacerbating damage of systemic organs or even death in the early phase of SAP [13,14].…”

Section: Discussionmentioning

confidence: 99%

Immune Dysregulation in Patients with Severe Acute Pancreatitis

et al. 2010

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To investigate patients with severe acute pancreatitis (SAP) by dynamic levels of pro-/anti-inflammatory cytokines and endotoxin (ET) in plasma and the relationship between immunity and infection, organ dysfunction. Seventy-two patients with SAP were recruited. The ET, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-10 (IL-10), and interleukin-4 (IL-4) were determined on admission and days 3, 7, and 14. For comparison, patients were analyzed through infection group versus non-infection group, multiple organ dysfunction syndrome (MODS) group versus non-MODS group. There were sixteen patients with secondary infection, twenty-two with MODS, and nine deaths. The infection group had higher levels of ET than the non-infection group on days 3 and 7. The dynamic cytokine levels of patients in the MODS group were unanimous with those outcomes in the infection group. The levels of cytokines in the infection group were different from the non-infection group, with more levels of TNF-α, IL-6 on days 3 and 7 and less on days 14, and more levels of IL-10, IL-4 on days 7 and 14. The levels of TNF-α, IL-6 in the MODS group were different from the non-MODS group, with more levels on days 3 and 7, and less levels on days 14. Immune dysregulation may play an important role in infection and organ dysfunction for patients with SAP.

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Section: Discussionmentioning

confidence: 99%

Immune Dysregulation in Patients with Severe Acute Pancreatitis

et al. 2010

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“…33 Acute pancreatitis, resulting from the inflammatory auto-digestion of the pancreas, is associated with high expression of Gαq in pancreatic tissue. 34 Many GPCRs, considered therapeutic targets for MS/EAE, are reported to be Gαq-coupled. The receptor cysLT1 is thought to predominantly couple with Gαq, and intracellular-extracellular calcium and Erk activation have been observed through the pathway.…”

Section: Discussionmentioning

confidence: 99%

Deficiency of the G protein Gαq ameliorates experimental autoimmune encephalomyelitis with impaired DC-derived IL-6 production and Th17 differentiation

et al. 2017

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Many G protein-coupled receptors (GPCRs) are reported to be involved in the pathogenesis of multiple sclerosis (MS), and ~40% of all identified GPCRs rely on the Gαq/11 G protein family to stimulate inositol lipid signaling. However, the function of Gα subunits in MS pathogenesis is still unknown. In this study, we attempted to determine the role of Gαq in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a well-known mouse model of MS. We discovered that compared with wild-type mice, Gαq-knockout mice exhibited less severe EAE symptoms, with lower clinical scores, reduced leukocyte infiltration and less extensive demyelination. Moreover, a significantly lower percentage of Th17 cells, one of the key players in MS pathogenesis, was observed in Gαq-knockout EAE mice. Studies in vitro demonstrated that deficiency of Gαq in CD4 T cells directly impaired Th17 differentiation. In addition, deficiency of Gαq significantly impaired DC-derived IL-6 production, thus inhibiting Th17 differentiation and the Gαq-PLCβ-PKC and Gαq-MAPKs signaling pathways involved in the reduced IL-6 production by DCs. In summary, our data highlighted the critical role of Gαq in regulating Th17 differentiation and MS pathogenesis.

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“…7 A large proportion of GPCRs rely on Gαq, making this family a broad player in the regulation of physiological functions. With relevance to disease, blocking Gαq ameliorates murine lupus, 8 with overexpression of Gαq linked to pancreatitis, 9 indicating a role for Gαq signaling in disease pathogenesis. In support of this, Gαq is a well-characterized player in the mechanisms driving MS, including the regulation of T-cell survival 10 and migration, 11 and a body of data indicates that targeting Gαq-coupled signaling may by a therapeutic avenue in MS. 12,13 In the present issue of Cellular and Molecular Immunology, Lai et al 14 targeted this link between Gαq signaling and MS using Gαq knockout animals in the EAE model.…”

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confidence: 99%