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Alterations of Toll-like Receptor 4 Expression on Peripheral Blood Monocytes During the Early Stage of Human Acute Pancreatitis

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Abstract

We sought to study Toll-like receptor 4 (TLR4) expression on peripheral blood mononuclear cells (PBMCs) during the early stage of human acute pancreatitis (AP). Thirty consecutive patients with acute pancreatitis admitted within 24 hr of onset of abdominal pain were enrolled prospectively in this study. Blood samples were taken by venipuncture at admission and on the third and seventh days after admission. PBMCs were isolated, and TLR4 and CD14 expression on PBMCs was detected by flow cytometer. Serum tumor necrosis factor (TNF)-α, interleukin, and lipase were detected simultaneously. Relations among these parameters were analysis. In mild AP, TLR4 expression increased on the first day of admission and then continued to decline for several days. On the seventh day, TLR4 expression was almost normal compared with that of the normal control. The alteration of serum TNF-α was coincidence with TLR4. We conclude that mononuclear-macrophages might be ignited through TLR4 (the gatekeeper of the innate immune system) and lead to production of TNF-α.

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References

  1. Steinberg W, Tenner S (1994) Acute pancreatitis. N Engl J Med 330(17): 1198–1210

    Article  PubMed  CAS  Google Scholar 

  2. Matzinger P (2002) The danger model: a renewed sense of self. Science 296(5566): 301–305

    Article  PubMed  CAS  Google Scholar 

  3. Denham W, Yang J, Norman J (1997) Evidence for an unknown component of pancreatic ascites that induces adult respiratory distress syndrome through an interleukin-1 and tumor necrosis factor-dependent mechanism. Surgery 122(2):295–301

    Article  PubMed  CAS  Google Scholar 

  4. Hietaranta A, Mustonen H, Puolakkainen P, et al. (2004) Proinflammatory effects of pancreatic elastase are mediated through TLR4 and NF-κB. Biochem Biophys Res Commun 323(1):192–196

    Article  PubMed  CAS  Google Scholar 

  5. Jaffray C, Yang J, Norman J (2000) Elastase mimics pancreatitis-induced hepatic injury via inflammatory mediators. J Surg Res 90(2):95–101

    Article  PubMed  CAS  Google Scholar 

  6. Closa D, Sabater L, Fernandez-Cruz L, Prats N, Gelpi E, Rosello-Catafau J (1999) Activation of alveolar macrophages in lung injury associated with experimental acute pancreatitis is mediated by the liver. Ann Surg 229(2):230–236

    Article  PubMed  CAS  Google Scholar 

  7. Johnson GB, Brunn GJ, Platt JL (2004) Cutting edge: an endogenous pathway to systemic inflammatory response syndrome (SIRS)-like reactions through Toll-like receptor 4. J Immunol 172(1):20–24

    PubMed  CAS  Google Scholar 

  8. Johnson GB, Brunn GJ, Kodaira Y, Platt JL (2002) Receptor-mediated monitoring of tissue well-being via detection of soluble heparan sulfate by Toll-like receptor 4. J Immunol 168(10):5233–5239

    PubMed  CAS  Google Scholar 

  9. Bradley EL 3rd (1993) A clinically based classification system for acute pancreatitis. Summary of the International Symposium on Acute Pancreatitis, Atlanta, Georgia, September 11 through 13, 1992. Arch Surg 128(5):586

    Google Scholar 

  10. Fink GW, Norman JG (1996) Intrapancreatic interleukin-1beta gene expression by specific leukocyte populations during acute pancreatitis. J Surg Res 63(1):369–373

    Article  PubMed  CAS  Google Scholar 

  11. Dugernier TL, Laterre PF, Wittebole X, et al. (2003) Compartmentalization of the inflammatory response during acute pancreatitis:correlation with local and systemic complications. Am J Respir Crit Care Med 168(2):148–157

    Article  PubMed  Google Scholar 

  12. Norman JG, Fink GW, Denham W, et al. (1997) Tissue-specific cytokine production during experimental acute pancreatitis. A probable mechanism for distant organ dysfunction. Dig Dis Sci 42(8):1783–1788

    Article  PubMed  CAS  Google Scholar 

  13. Denham W, Yang J, Fink G, Denham D, Carter G, Ward K, Norman J (1997) Gene targeting demonstrates additive detrimental effects of interleukin 1 and tumor necrosis factor during pancreatitis. Gastroenterology 113(5):1741–1746

    Article  PubMed  CAS  Google Scholar 

  14. Ikushima H, Nishida T, Takeda K, et al. (2004) Expression of Toll-like receptors 2 and 4 is downregulated after operation. Surgery 135(4):376–385

    Article  PubMed  Google Scholar 

  15. Dybdahl B, Wahba A, Lien E, et al. (2002) Inflammatory response after open heart surgery: release of heat-shock protein 70 and signaling through Toll-like receptor-4. Circulation 105(6):685–690

    Article  PubMed  CAS  Google Scholar 

  16. Gotzinger P, Sautner T, Spittler A, Barlan M, Wamser P, Roth E, Jakesz R, Fugger R (2000) Severe acute pancreatitis causes alterations in HLA-DR and CD14 expression on peripheral blood monocytes independently of surgical treatment. Eur J Surg 166(8):628–632

    Article  PubMed  CAS  Google Scholar 

  17. Satoh A, Miura T, Satoh K, Masamune A, Yamagiwa T, Sakai Y, Shibuya K, Takeda K, Kaku M, Shimosegawa T (2002) Human leukocyte antigen-DR expression on peripheral monocytes as a predictive marker of sepsis during acute pancreatitis. Pancreas 25(3):245–250

    Article  PubMed  Google Scholar 

  18. Mentula P, Kylanpaa ML, Kemppainen E, Jansson SE, Sarna S, Puolakkainen P, Haapiainen R, Repo H (2004) Plasma anti-inflammatory cytokines and monocyte human leucocyte antigen-DR expression in patients with acute pancreatitis. Scand J Gastroenterol 39(2):178–187

    Article  PubMed  CAS  Google Scholar 

  19. Li Y, Zhou ZG, Xia QJ, Zhang J, Li HG, Cao GQ, Wang R, Lu YL, Hu TZ (2005) Toll-like receptor 4 detected in exocrine pancreas and the change of expression in cerulein-induced pancreatitis. Pancreas 30(4):375–381

    Article  PubMed  CAS  Google Scholar 

  20. Chen CC, Wang SS, Lee FY, Chang FY, Lee SD (1999) Proinflammatory cytokines in early assessment of the prognosis of acute pancreatitis. Am J Gastroenterol 94(1):213–218

    Article  PubMed  CAS  Google Scholar 

  21. Pezzilli R, Billi P, Miglioli M, Gullo L (1993) Serum amylase and lipase concentrations and lipase/amylase ratio in assessment of etiology and severity of acute pancreatitis. Dig Dis Sci 38:1265–1269

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

This work was supported by the National Nature-Science Foundation (30400434) and National Outstanding Youth Foundation of China (39925032)

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Correspondence to Zong-Guang Zhou.

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Li, HG., Zhou, ZG., Li, Y. et al. Alterations of Toll-like Receptor 4 Expression on Peripheral Blood Monocytes During the Early Stage of Human Acute Pancreatitis. Dig Dis Sci 52, 1973–1978 (2007). https://doi.org/10.1007/s10620-006-9211-4

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  • DOI: https://doi.org/10.1007/s10620-006-9211-4

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