Interleukin-22 ameliorates acute severe pancreatitis-associated lung injury in mice.
OBJECTIVE
To investigate the potential protective effect of exogenous recombinant interleukin-22 (rIL-22) on L-arginine-induced acute severe pancreatitis (SAP)-associated lung injury and the possible signaling pathway involved.


METHODS
Balb/c mice were injected intraperitoneally with L-arginine to induce SAP. Recombinant mouse IL-22 was then administered subcutaneously to mice. Serum amylase levels and myeloperoxidase (MPO) activity in the lung tissue were measured after the L-arginine administration. Histopathology of the pancreas and lung was evaluated by hematoxylin and eosin (HE) staining. Expression of B cell lymphoma/leukemia-2 (Bcl-2), Bcl-xL and IL-22RA1 mRNAs in the lung tissue was detected by real-time PCR. Expression and phosphorylation of STAT3 were analyzed by Western blot.


RESULTS
Serum amylase levels and MPO activity in the lung tissue in the SAP group were significantly higher than those in the normal control group (P < 0.05). In addition, the animals in the SAP group showed significant pancreatic and lung injuries. The expression of Bcl-2 and Bcl-xL mRNAs in the SAP group was decreased markedly, while the IL-22RA1 mRNA expression was increased significantly relative to the normal control group (P < 0.05). Pretreatment with PBS did not significantly affect the serum amylase levels, MPO activity or expression of Bcl-2, Bcl-xL or IL-22RA1 mRNA (P > 0.05). Moreover, no significant differences in the degrees of pancreatic and lung injuries were observed between the PBS and SAP groups. However, the serum amylase levels and lung tissue MPO activity in the rIL-22 group were significantly lower than those in the SAP group (P < 0.05), and the injuries in the pancreas and lung were also improved. Compared with the PBS group, rIL-22 stimulated the expression of Bcl-2, Bcl-xL and IL-22RA1 mRNAs in the lung (P < 0.05). In addition, the ratio of p-STAT3 to STAT3 protein in the rIL-22 group was significantly higher than that in the PBS group (P < 0.05).


CONCLUSIONS
Exogenous recombinant IL-22 protects mice against L-arginine-induced SAP-associated lung injury by enhancing the expression of anti-apoptosis genes through the STAT3 signaling pathway.
Ying-Ying Qiao, Xiao-Qin Liu, Chang-Qin Xu, Zheng Zhang, Hong-Wei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China.
Ying-Ying
YY
Qiao
Ying-Ying Qiao, Xiao-Qin Liu, Chang-Qin Xu, Zheng Zhang, Hong-Wei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China.
Xiao-Qin
XQ
Liu
Ying-Ying Qiao, Xiao-Qin Liu, Chang-Qin Xu, Zheng Zhang, Hong-Wei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China.
Chang-Qin
CQ
Xu
Ying-Ying Qiao, Xiao-Qin Liu, Chang-Qin Xu, Zheng Zhang, Hong-Wei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China.
Zheng
Z
Zhang
Ying-Ying Qiao, Xiao-Qin Liu, Chang-Qin Xu, Zheng Zhang, Hong-Wei Xu, Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong Province, China.
Hong-Wei
HW
Xu
D000208:Acute Disease; D055371:Acute Lung Injury / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D000681:Amylases / Q000097:blood; D000818:Animals; D001120:Arginine; D015415:Biomarkers / Q000097:blood; D015153:Blotting, Western; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007378:Interleukins / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008807:Mice, Inbred BALB C; D010179:Pancreas / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009195:Peroxidase / Q000097:blood; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050796:STAT3 Transcription Factor / Q000378:metabolism; D012720:Severity of Illness Index; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051020:bcl-X Protein / Q000235:genetics / Q000378:metabolism; D000097043:Interleukin-22
D000681:Amylases; D001120:Arginine; D015415:Biomarkers; D007378:Interleukins; D009195:Peroxidase; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D050796:STAT3 Transcription Factor; D051020:bcl-X Protein; D000097043:Interleukin-22; C494812:Bcl2l1 protein, mouse; C494087:Stat3 protein, mouse; C415369:interleukin-22 receptor; C052617:Bcl2 protein, mouse
Acute severe pancreatitis; Anti-apoptosis gene; Interleukin-22; Lung injury; Signal transducer and activator of transcription 3