Decreased expression of Toll-like receptor 2 and 4 on macrophages in experimental severe acute pancreatitis
Related Experiment Video
Updated: Jul 8, 2026
Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection
Published on: May 10, 2024
Naoki Matsumura1, Yoshifumi Takeyama, Takashi Ueda
1Division of Gastroenterological Surgery, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Abstract:
In severe acute pancreatitis (SAP), immunologic impairment in the early phase may be linked to subsequent infectious complications that are main contributor to the high mortality. Toll-like receptors (TLRs) recognize microorganisms as the innate immune system, and are involved in host defense mechanism. TLR2 recognizes lipoteichoic acid (LTA) of gram-positive bacteria, and TLR4 recognizes lipopolysaccharide (LPS) of gram-negative bacilli. This study aimed to investigate the expression of TLRs on macrophages and their TLRs-mediated cytokine production in rat SAP. SAP was induced by retrograde injection of 3% sodium deoxycholate into the biliopancreatic duct in male Wistar rats. Macrophages were isolated from bronchoalveolar lavage fluid 6 hours after induction of SAP. The expression of TLR2 and TLR4 was analyzed by real-time RT-PCR and western blotting. TNF-alpha release from macrophages was estimated after 4-hour stimulation of LTA or LPS. Endotoxin/bacterial translocation (E/BT) was also evaluated in this model. The expression of TLR2 (mRNA and protein) and LTA-mediated TNF-alpha production were significantly decreased in SAP compared with control. The expression of TLR4 (mRNA and protein) and LPS-mediated TNF-alpha production was also significantly decreased in SAP compared with control. E/BT occurred 18 hours after induction of SAP. These results suggest that the impaired responsiveness to LTA and LPS of macrophages is derived from decreased expression of TLR2 and TLR4, respectively. This suppression of immune response in the early phase may be implicated in the mechanism of infectious complications.
Insights
Severe acute pancreatitis (SAP) impairs macrophage Toll-like receptors (TLRs), specifically TLR2 and TLR4, reducing cytokine production and potentially increasing infectious complications. This early immune suppression in SAP warrants further investigation.
Area of Science:
- Immunology
- Gastroenterology
- Critical Care Medicine
Background:
- Severe acute pancreatitis (SAP) is associated with immune dysfunction and high mortality, often due to infectious complications.
- Toll-like receptors (TLRs) are crucial for innate immunity, recognizing bacterial components like lipoteichoic acid (LTA) via TLR2 and lipopolysaccharide (LPS) via TLR4.
- Early immune impairment in SAP may predispose patients to subsequent infections.
Purpose of the Study:
- To investigate the expression of Toll-like receptors (TLRs) on macrophages in a rat model of severe acute pancreatitis (SAP).
- To assess the impact of SAP on TLR-mediated cytokine production by macrophages.
- To explore the relationship between TLR expression, cytokine response, and bacterial translocation in early SAP.
Main Methods:
- Severe acute pancreatitis (SAP) was induced in male Wistar rats via retrograde biliopancreatic duct injection of sodium deoxycholate.
- Macrophages were isolated from bronchoalveolar lavage fluid 6 hours post-induction.
- TLR2 and TLR4 expression (mRNA and protein) were quantified using real-time RT-PCR and Western blotting; TNF-alpha release was measured after LTA or LPS stimulation; endotoxin/bacterial translocation (E/BT) was evaluated.
Main Results:
- A significant decrease in both TLR2 and TLR4 expression (mRNA and protein) was observed in macrophages from SAP rats compared to controls.
- Macrophage stimulation with LTA or LPS resulted in significantly reduced TNF-alpha production in the SAP group.
- Endotoxin/bacterial translocation (E/BT) was detected 18 hours after SAP induction.
Conclusions:
- The study demonstrates impaired expression and responsiveness of TLR2 and TLR4 on macrophages during the early phase of severe acute pancreatitis (SAP) in rats.
- This suppressed immune response, characterized by reduced TLR expression and cytokine production, may contribute to the increased susceptibility to infectious complications in SAP.
- These findings highlight a potential mechanism linking early immune dysregulation to poor outcomes in severe acute pancreatitis.
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