Blockade of JAK2 signaling produces immunomodulatory effect to preserve pancreatic homeostasis in severe acute pancreatitis

Qiu, Zhaolei; Xu, Feng; Wang, Zhenjie; Yang, Peng; Zhang, Bu; Cheng, Feng; Jiang, Hai; Li, Lei; Zhang, Fulong

doi:10.1016/j.bbrep.2021.101133

Cited by 4 publications

(3 citation statements)

References 29 publications

(28 reference statements)

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“…In most studies, however, activation of STAT3 stimulates macrophage M2 polarization. According to one study, JAK2/STAT3 activity was significantly increased in rats with severe acute pancreatitis, and JAK2 inhibition increased levels of cytokines (such as Foxp3, IL-10, and TGF-β) necessary for M2 macrophage polarization, leading to a reduction in the secretion of pro-inflammatory factors IL-6, IFN-γ, and TNF-α, which prevents pancreatic inflammation and damage ( 40 ). In animal models of myocardial ischemia/reperfusion injury and psoriasis, it was also demonstrated that inhibition of the JAK/STAT3 signaling pathway promoted macrophage M2 polarization, which in turn reduced pro-inflammatory factors and upregulated anti-inflammatory and pro-fibrotic factor levels, thereby favorably alleviating tissue inflammation and inhibiting tissue damage ( 41 , 42 ).…”

Section: Research On the Signaling Pathways Related To Stat3 Regulati...mentioning

confidence: 99%

Advances in the role of STAT3 in macrophage polarization

et al. 2023

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The physiological processes of cell growth, proliferation, differentiation, and apoptosis are closely related to STAT3, and it has been demonstrated that aberrant STAT3 expression has an impact on the onset and progression of a number of inflammatory immunological disorders, fibrotic diseases, and malignancies. In order to produce the necessary biological effects, macrophages (M0) can be polarized into pro-inflammatory (M1) and anti-inflammatory (M2) types in response to various microenvironmental stimuli. STAT3 signaling is involved in macrophage polarization, and the research of the effect of STAT3 on macrophage polarization has gained attention in recent years. In order to provide references for the treatment and investigation of disorders related to macrophage polarization, this review compiles the pertinent signaling pathways associated with STAT3 and macrophage polarization from many fundamental studies.

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Section: Research On the Signaling Pathways Related To Stat3 Regulati...mentioning

confidence: 99%

Advances in the role of STAT3 in macrophage polarization

et al. 2023

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“…STAT pathway up-regulation inflammation (32,33) resulting in persistent and intensified inflammation (26). TLR9 is expressed in resident immune cells of the pancreas, which are predominantly represented by macrophages, and it is an important DAMP receptors upstream of inflammasome activation, and caspase-1, and NLRP3 inflammasome are required for the development of inflammation in AP (20,27).…”

Section: The Mechanism Of Acute Pancreatitismentioning

confidence: 99%

The Mechanism of Lung and Intestinal Injury in Acute Pancreatitis: A Review

Liu¹,

Wen²,

Wang³

et al. 2022

Front. Med.

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Acute pancreatitis (AP), as a common cause of clinical acute abdomen, often leads to multi-organ damage. In the process of severe AP, the lungs and intestines are the most easily affected organs aside the pancreas. These organ damages occur in succession. Notably, lung and intestinal injuries are closely linked. Damage to ML, which transports immune cells, intestinal fluid, chyle, and toxic components (including toxins, trypsin, and activated cytokines to the systemic circulation in AP) may be connected to AP. This process can lead to the pathological changes of hyperosmotic edema of the lung, an increase in alveolar fluid level, destruction of the intestinal mucosal structure, and impairment of intestinal mucosal permeability. The underlying mechanisms of the correlation between lung and intestinal injuries are inflammatory response, oxidative stress, and endocrine hormone secretion disorders. The main signaling pathways of lung and intestinal injuries are TNF-α, HMGB1-mediated inflammation amplification effect of NF-κB signal pathway, Nrf2/ARE oxidative stress response signaling pathway, and IL-6-mediated JAK2/STAT3 signaling pathway. These pathways exert anti-inflammatory response and anti-oxidative stress, inhibit cell proliferation, and promote apoptosis. The interaction is consistent with the traditional Chinese medicine theory of the lung being connected with the large intestine (fei yu da chang xiang biao li in Chinese). This review sought to explore intersecting mechanisms of lung and intestinal injuries in AP to develop new treatment strategies.

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“…The incidence of AP continues to increase, causing single or multiple organ failure [7,8,9]. Pulmonary complications occupy a special place among the consequences of AP [1,6,13,14]. It has been established that in the pathogenesis of lung pathology, the morphofunctional state of type II alveolocytes plays an important role.…”

Section: Introductionmentioning

confidence: 99%

Submicroscopic changes of type II alveolocytes in the late development of experimental acute pancreatitis

Zaiats,

Pasichnyk,

Zukow

2024

J Educ Health Sport

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Background. Today, acute pancreatitis is one of the most common and severe visceral disorders in patients worldwide. The aim of the work was to study the dynamics of ultrastructural changes of type II alveolocytes in the long-term periods of development of experimental acute pancreatitis. Material and methods. The experiments were carried out on 54 white Wistar male rats weighing 180–220 g. The animals were divided into three groups: first — intact, second — control, third — experimental with a model of acute pancreatitis, which was reproduced by intraperitoneal administration of a 20% solution of L-arginine at a total dose of 5 g/kg at one-hour interval. The control group of animals was intraperitoneally injected with an equivalent dose of isotonic sodium chloride solution. All research were performed under sodium thiopental anesthesia at the rate of 60 mg/kg body weight. Lung tissue for electron microscopic examination was collected from the lower lobe of the left lung at 3–5 and 7 days. Pieces of lung tissue measuring 1×1×1 mm were fixed in a 2.5% glutaraldehyde solution, followed by additional fixation in a 1% osmium tetroxide solution. After dehydration, the material was poured into Epon-Araldite. Sections with a thickness of 20–50 nm obtained on “Tesla BS-490” ultramicrotome were studied in a PEM-125K electron microscope. Results. It was found that three days after the start of the study, along with dystrophic-destructive changes, type II alveolocytes in a state of increased functional activity were observed. Continuation of the experiment (5 days) leads to the progression of ultrastructural changes in type II alveolocytes are determined, which are most pronounced on the 7 day of the study. Conclusion. Acute experimental pancreatitis is accompanied by marked changes in the ultrastructural structure of type II alveolocytes. The nature and severity of structural changes of type II alveolocytes depends on the duration of the course of arginine-induced acute pancreatitis.

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Blockade of JAK2 signaling produces immunomodulatory effect to preserve pancreatic homeostasis in severe acute pancreatitis

Cited by 4 publications

References 29 publications

Advances in the role of STAT3 in macrophage polarization

Advances in the role of STAT3 in macrophage polarization

The Mechanism of Lung and Intestinal Injury in Acute Pancreatitis: A Review

Submicroscopic changes of type II alveolocytes in the late development of experimental acute pancreatitis

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