Signal Pathways and Markers Involved in Acute Lung Injury Induced by Acute Pancreatitis

Abstract

Acute pancreatitis (AP) is a common acute abdominal disease with a mortality rate of about 30%. Acute lung injury (ALI) is a common systemic complication of acute pancreatitis, with progressive hypoxemia and respiratory distress as the main manifestations, which can develop into acute respiratory distress syndrome or even multiple organ dysfunction syndrome (MODS) in severe cases, endangering human health. In the model of AP, pathophysiological process of the lung can be summarized as oxidative stress injury, inflammatory factor infiltration, and alveolar cell apoptosis. However, the intrinsic mechanisms underlying AP and how it leads to ALI are not fully understood. In this paper, we summarize recent articles related to AP leading to ALI, including the signal transduction pathways and biomarkers of AP-ALI. There are factors or pathway aggravating ALI, the JAK2-STAT3 signaling pathway, NLRP3/NF-κB pathway, mitogen-activated protein kinase, PKC pathway, neutrophil protease (NP)-LAMC2-neutrophil pathway, and the P2X7 pathway, and there are important transcription factors in the NRF2 signal transduction pathway which could give researchers better understanding of the underlying mechanisms controlling AP and ALI and lay the foundation for finally curing ALI induced by AP.

Thioredoxin-interacting protein deficiency protects against severe acute pancreatitis by suppressing apoptosis signal-regulating kinase 1

“…In severe cases, systemic inflammation and failure of the surrounding organs will occur [ 27 , 28 ]. The inflammatory response and oxidative stress play an indispensable role in SAP [ 20 , 22 ]. TXNIP is a multi-functional protein that acts as a signal conductor of the oxidative stress response [ 29 ].…”

“…Activated PSCs also secrete the neutrophil chemokine IL-8 and macrophage chemoattractant protein-1 (MCP-1) and express intracellular adhesion molecule-1 (ICAM-1) [ 36 , 37 ], suggesting that activated PSCs may be involved in exacerbating pancreatic inflammation by recruiting inflammatory cells. Studies have shown that pancreatic acinar cells secrete various inflammatory cytokines in response to the stimulation of pancreatitis [ 16 , 20 ]. The inflammatory response during SAP is characterized by the induction of a cascade of proinflammatory mediators which culminates in the recruitment of macrophages and neutrophils to the inflamed pancreas, thus leading to pancreatic acinar cell injury [ 38 ].…”

“…However, the role of TXNIP in SAP has yet to be evaluated. Therefore, TXNIP is an important molecule connecting various cellular functional pathways in oxidative stress and inflammation [ 20 , 21 ]. However, the role of TXNIP in SAP has yet to be evaluated.…”

Thioredoxin-interacting protein deficiency protects against severe acute pancreatitis by suppressing apoptosis signal-regulating kinase 1

“…Another study showed that melatonin alleviates lung inflammation caused by silica nanoparticles by downregulating TXNIP-related signaling pathways [11] . Therefore, TXNIP is an important molecule connecting various cellular functional pathways in oxidative stress and inflammation [12,13] . However, the role of TXNIP in SAP has yet to be evaluated.…”

Ulinastatin ameliorates acute pancreatitis and associated intestinal and pulmonary injury by inhibiting NLRP3 inflammatory vesicles and affecting intestinal flora composition and metabolic pathways in rat

“…NLRP3, one of the NLR proteins, plays an important role in forming in ammasomes, which mediate caspase−1 activation and the secretion of the proin ammatory cytokine IL−1β in response to microbial infection and cellular damage [3]. It has been shown that NLRP3 in ammatory vesicles are activated not only in the pancreas but also in the intestine and lungs of rats with AP, and that the degree of activation correlates with the severity of AP [4] [5]. Effective inhibition of the NLRP3 pathway has emerged as an effective means of treating the in ammatory response to AP.…”