Effects of Tec Tyrosine Kinase Inhibition on the Inflammatory Response of Severe Acute Pancreatitis-Associated Acute Lung Injury in Mice

Abstract

Background: The Tec kinase family is involved in acute and chronic inflammatory diseases, but its relationship with severe acute pancreatitis (SAP) remains unclear.

Aims: To investigate whether Tec tyrosine kinase can be used as a target for severe acute pancreatitis-associated acute lung injury (PALI).

Methods: A total of 90 mice were randomly assigned into four groups: SAP (n = 15), control (n = 15), SAP + α-cyano-β-hydroxy-β-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13) (pretreated with Tec kinase inhibitor LFM-A13, n = 15), and SAP + Tec siRNA (pretreated with PBS/negative control siRNA/Tec siRNA, n = 45). SAP was induced by caerulein and lipopolysaccharide. Animals were sacrificed at 0, 3, 24, 48, and 72 h, respectively. Pathological changes and scores of the lung and pancreas were determined using hematoxylin-eosin staining. Expression of Tec and phosphorylated Tec (p-Tec) were examined by real-time polymerase chain reaction, Western blot, and immunoprecipitation. Serum levels of amylase, myeloperoxidase, and pro-inflammatory cytokines were measured by ELISA.

Results: The expression of Tec in lung tissue was significantly higher in the SAP group than in the control group (p < 0.05), and p-Tec expression gradually increased with time. Furthermore, p-Tec expression was significantly lower in the SAP + LFM-A13 group than in the SAP group (p < 0.05); however, Tec expression did not vary. Tec inhibitors, LFM-A13 and Tec siRNA, alleviated pathological damage and release of inflammatory cytokines (p < 0.05).

Conclusions: Tec tyrosine kinase plays a key role in PALI, and is therefore a potential target for clinical treatment.

Keywords: Acute lung injury; LFM-A13; Severe acute pancreatitis; Tec tyrosine kinase; siRNA.