Skip to main content
SpringerLink
Log in

Role of Intrapulmonary Expression of Inducible Nitric Oxide Synthase Gene and Nuclear Factor κB Activation in Severe Pancreatitis-associated Lung Injury

  • Published:
Inflammation Aims and scope Submit manuscript

Abstract

The aim of this study is to explore the relationship of intrapulmonary activation of nuclear factor-κB (NF-κB) and the expression of inducible nitric oxide synthase (iNOS) mRNA with pulmonary injury in rats with severe acute pancreatitis (SAP). Fifty-four Sprague Dawley rats were randomly divided into three groups: sham operation (control) group (n = 18), SAP group (n = 18), and pyrrolindine dithiocarbamate (PDTC) pretreated group (n = 18). A SAP model was induced by retrograde injected 5% sodium taurocholate into the bile-pancreatic duct (1 ml/kg). PDTC-pretreated SAP rats were given 100 mg/kg body weight PDTC intraperitoneally before pancreatitis was induced. Six rats from each group were sacrificed at 3, 6, and 12 h after modeling. Activation of NF-κB in pulmonary tissues and pancreas tissues was detected by immunohistochemical methods. Intrapulmonary expression of iNOSmRNA was assayed by fluorogenic quantitative reverse transcription polymerize chain reaction. The expression of NF-κB in the SAP group in pulmonary tissues was enhanced significantly at any measure point compared with control group (58.4 ± 10.8 vs. 3.8 ± 1.8, 119.8 ± 17.8 vs. 5.2 ± 2.4, and 90.2 ± 14.4 vs. 4.7 ± 2.2, P < 0.01). But the expressions of NF-κB in the PDTC group were significantly lower than those in SAP group (54.3 ± 9.6 vs. 58.4 ± 10.8, 93.9 ± 7.9 vs. 119.8 ± 17.8, and 82.2 ± 13.3 vs. 90.2 ± 14.4, P < 0.05). The number of positive cells in SAP group and PDTC group reached its peak at 6 h and then declined. The expression of iNOSmRNA in PDTC groups was significantly weaker than that in SAP group (2.0 ± 0.8 vs. 2.2 ± 1.9, 2.4 ± 1.2 vs. 4.6 ± 1.8, and 1.5 ± 0.8 vs. 3.2 ± 1.5, P < 0.05). The activation of NF-κB may be involved in the SAP lung injury through regulating the expression of iNOSmRNA. PDTC might inhibit the activation of NF-κB and then reduce the expression of iNOSmRNA and effectively alleviate the severity of lung injury.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Algul, H., M. Treiber, M. Lesina, H. Nakhai, D. Saur, F. Geisler, A. Pfeifer, S. Paxian, and R.M. Schmid. 2007. Pancreas-specific RelA/p65 truncation increases susceptibility of acini to inflammation-associated cell death following cerulein pancreatitis. Journal of Clinical Investigation 117: 1490–1501.

    Article  PubMed  CAS  Google Scholar 

  2. Renzulli, P., S.M. Jakob, M. Tauber, D. Candinas, and B. Gloor. 2005. Severe acute pancreatitis: case-oriented discussion of interdisciplinary management. Pancreatology 5: 145–156.

    Article  PubMed  Google Scholar 

  3. Hirota, M., H. Sugita, K. Maeda, A. Ichibara, and M. Ogawa. 2004. Concept of SIRS and severe acute pancreatitis. Nippon Rinsho 62: 2128–2136.

    PubMed  Google Scholar 

  4. Surbatovic, M., K. Jovanovic, S. Radakovic, and N. Filipovic. 2005. Pathophysiological aspects of severe acute pancreatitis-associated lung injury. Srpski Arhiv za Celokupno Lekarstvo 133: 76–81.

    Article  PubMed  Google Scholar 

  5. Rakonczay Jr., Z., P. Hegyi, T. Takacs, J. McCarroll, and A.K. Saluja. 2008. The role of NF-kappaB activation in the pathogenesis of acute pancreatitis. Gut 57: 259–267.

    Article  CAS  PubMed  Google Scholar 

  6. Gray, K.D., M.O. Simovic, T.S. Blackwell, J.W. Christman, A.K. May, K.S. Parman, W.C. Chapman, and S.C. Stain. 2006. Activation of nuclear factor kappa B and severe hepatic necrosis may mediate systemic inflammation in choline-deficient/ethionine-supplemented diet-induced pancreatitis. Pancreas 33: 260–267.

    Article  CAS  PubMed  Google Scholar 

  7. Pang, H.Y., G. Liu, and G.T. Liu. 2009. Compound FLZ inhibits lipopolysaccharide-induced inflammatory effects via down-regulation of the TAK-IKK and TAK-JNK/p38MAPK pathways in RAW264.7 macrophages. Acta Pharmacologica Sinica 30: 209–218.

    Article  CAS  PubMed  Google Scholar 

  8. Zhang, X.P., L. Zhang, L.J. Chen, Q.H. Cheng, J.M. Wang, W. Cai, H.P. Shen, and J. Cai. 2007. Influence of dexamethasone on inflammatory mediators and NF-kappaB expression in multiple organs of rats with severe acute pancreatitis. World Journal of Gastroenterology 13: 548–556.

    Article  PubMed  Google Scholar 

  9. Ang, A.D., S. Adhikari, S.W. Ng, and M. Bhatia. 2008. Expression of nitric oxide synthase isoforms and nitric oxide production in acute pancreatitis and associated lung injury. Pancreatology 9: 150–159.

    Article  PubMed  CAS  Google Scholar 

  10. Aho, H.J., and T.J. Nevalainen. 1980. Experimental pancreatitis in the rat. Ultrastructure of sodium taurocholate-induced pancreatic lesions. Scandinavian Journal of Gastroenterology 15: 417–424.

    Article  CAS  PubMed  Google Scholar 

  11. Schmittgen, T.D., and K.J. Livak. 2008. Analyzing real-time PCR data by the comparative C(T) method. Nature Protocols 3: 1101–1108.

    Article  CAS  PubMed  Google Scholar 

  12. Wang, G., B. Sun, Y. Gao, Q.H. Meng, and H.C. Jiang. 2007. The effect of emodin-assisted early enteral nutrition on severe acute pancreatitis and secondary hepatic injury. Mediators of Inflammation 2007: 29638.

    PubMed  Google Scholar 

  13. Zhang, X.P., L. Zhang, H.M. Xu, Y.P. Xu, Q.H. Cheng, J.M. Wang, and H.P. Shen. 2008. Application of tissue microarrays to study the influence of dexamethasone on NF-kappaB expression of pancreas in rat with severe acute pancreatitis. Digestive Diseases and Sciences 53: 571–580.

    Article  CAS  PubMed  Google Scholar 

  14. Karin, M. 2006. Nuclear factor-kappaB in cancer development and progression. Nature 441: 431–436.

    Article  CAS  PubMed  Google Scholar 

  15. Liu, Y., K. Kimura, R. Yanai, T. Chikama, and T. Nishida. 2008. Cytokine, chemokine, and adhesion molecule expression mediated by MAPKs in human corneal fibroblasts exposed to poly(I:C). Investigative Ophthalmology and Visual Science 49: 3336–3344.

    Article  PubMed  Google Scholar 

  16. Choi, Y.S., J. Hur, and S. Jeong. 2007. Beta-catenin binds to the downstream region and regulates the expression C-reactive protein gene. Nucleic Acids Research 35: 5511–5519.

    Article  CAS  PubMed  Google Scholar 

  17. van Erp, K., K. Dach, I. Koch, J. Heesemann, and R. Hoffmann. 2006. Role of strain differences on host resistance and the transcriptional response of macrophages to infection with Yersinia enterocolitica. Physiological Genomics 25: 75–84.

    Article  PubMed  CAS  Google Scholar 

  18. Zhang, Y., C.X. Shi, and Y.X. Li. 2005. Effect of Salviae miltiorrhizae on mRNA expression of inducible nitric oxide synthase and organ injury in rats with severe acute pancreatitis. Zhongguo Zhong Xi Yi Jie He Za Zhi 25: 1012–1015.

    PubMed  Google Scholar 

  19. Leindler, L., E. Morschl, F. Laszlo, Y. Mandi, T. Takacs, K. Jarmai, and G. Farkas. 2004. Importance of cytokines, nitric oxide, and apoptosis in the pathological process of necrotizing pancreatitis in rats. Pancreas 29: 157–161.

    Article  CAS  PubMed  Google Scholar 

  20. Satoh, A., T. Shimosegawa, K. Kimura, S. Moriizumi, A. Masamune, M. Koizumi, and T. Toyota. 1998. Nitric oxide is overproduced by peritoneal macrophages in rat taurocholate pancreatitis: the mechanism of inducible nitric oxide synthase expression. Pancreas 17: 402–411.

    Article  CAS  PubMed  Google Scholar 

  21. Li, Y.Q., Z.X. Zhang, Y.J. Xu, W. Ni, S.X. Chen, Z. Yang, and D. Ma. 2006. N-Acetyl-L-cysteine and pyrrolidine dithiocarbamate inhibited nuclear factor-kappaB activation in alveolar macrophages by different mechanisms. Pharmacologica Sinica 27: 339–346.

    Article  CAS  Google Scholar 

Download references

Acknowledgment

This research is supported by the Program for New Century Excellent Talents in University (No. NCET-08-0876), the Educational Commission of Shandong Province (No. J08LJ53), the Health Commission of Shandong Province (No.2007HW034), the Binzhou Medical University (No. BY2007KJ25), the Natural Science Foundation of Sichuan Province (No. 2004A062), and the Natural Science Foundation of Shandong (No. Y2008C18, No. ZR0805350128)

Author information

Authors and Affiliations

  1. Department of Human Anatomy, Binzhou Medical University, No. 346 Guanhai Road, Yantai, 264003, China

    Shi-hai Kan & Fei Huang

  2. Department of Human Anatomy, Luzhou Medical College, Zhongshan Road, Luzhou, 646000, China

    Yun Gao & Chong-lin Yu

  3. Department of Laboratory Medicine, Yantai Economic and Technological Development Zone Hospital, Yantai, 264003, China

    Jing Tang

Authors
  1. Shi-hai Kan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fei Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jing Tang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yun Gao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Chong-lin Yu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Chong-lin Yu.

Additional information

Shi-hai Kan and Fei Huang contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kan, Sh., Huang, F., Tang, J. et al. Role of Intrapulmonary Expression of Inducible Nitric Oxide Synthase Gene and Nuclear Factor κB Activation in Severe Pancreatitis-associated Lung Injury. Inflammation 33, 287–294 (2010). https://doi.org/10.1007/s10753-010-9184-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10753-010-9184-5

KEY WORDS

Search

Navigation