Fractalkine and TGF-β1 levels reflect the severity of chronic pancreatitis in humans

Abstract

AIM:To clarify whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of chronic pancreatitis (CP). This study aimed at clarifying whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of CP. METHODS: Serum monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta-1 (TGF-β1), and soluble type fractalkine (s-fractalkine) concentrations were examined in patients with CP (n = 109) and healthy controls (n = 116). Severity of disease was classified in patients with CP by a staging system. Relationships between stage-specific various clinical factors and serum MCP-1, TGF-β1, and s-fractalkine levels were investigated. Furthermore, 57 patients with non-alcoholic CP were similarly evaluated in order to exclude influence of alcohol intake. RESULTS: Patients with CP showed significant higher levels of serum TGF-β1 and s-fractalkine, but not MCP-1, compared to the controls. Serum TGF-β1 in the severe stage and s-fractalkine in the mild and the severe stage of CP significantly increased compared to those of controls. However, it was observed that both TGF-β1 and s-fractalkine levels were affected by alcohol intake. In patients with non-alcoholic CP, serum TGF-β1 showed significant increase in the moderate stage of CP, and serum s-fractalkine revealed significant increase in the early stage of CP. CONCLUSION: It is suggested that the measurement of serum F-fractalkine is useful to diagnose earlystage CP. Moreover, the combined determination of both, s-fractalkine and TGF-β1, in human sera may be helpful in evaluating the severity status of CP.

ERK pathway and sheddases play an essential role in ethanol-induced CX3CL1 release in pancreatic stellate cells

“…This result supported previous study results and indicated that pancreatic tissue injury and various environmental factors promote CX3CL1 expression in the whole pancreas, so that connection of membrane-bound CX3CL1 and CX3CL1 receptors of inflammatory cells in the pancreatic tissue serves as the basis of the inflammation in CP as it does in chronic hepatitis. 11,17,18,36,37 Furthermore, sheddase is essential for CX3CL1 secretion into the blood. The abundant expression of sheddase in PSCs, as in hepatic stellate cells, 34 indicates that MMP not only enhances extracellular matrix degradation but also induces inflammation by CX3CL1 secretion.…”

“…50 The finding that both ethanol and acetaldehyde promoted MMP-2 secretion, but that acetaldehyde induced no synergetic secretion, supports the idea that MMP-9, instead of MMP-2, might be involved in the shedding of CX3CL1. The increased CX3CL1 concentration reported in the blood of drinkers probably reflects such mechanisms, 17 and cessation of alcohol abuse as treatment would be expected to inhibit the synergistic secretion of CX3CL1. Withdrawal of alcohol has been associated with regression of LPS-induced pancreatic injury in alcohol-fed rats, where decreased serum CX3CL1 levels might be observed.…”

“…We have already reported that the serum concentration of CX3CL1 in patients with CP correlates with clinical CP scores and that CX3CL1 is a useful biological marker for early detection of CP because it is secreted in the early stage of the disease. 17 The concentration of CX3CL1 is increased in chronic drinkers with CP at any stage of the disease, which suggests that the increase is also associated with alcohol consumption. 17 Increased expression of CX3CL1 in pancreatic tissue in human CP has also been correlated with pain scores.…”

“…17 The concentration of CX3CL1 is increased in chronic drinkers with CP at any stage of the disease, which suggests that the increase is also associated with alcohol consumption. 17 Increased expression of CX3CL1 in pancreatic tissue in human CP has also been correlated with pain scores. 18 As excessive expression and secretion of CX3CL1 has also been observed in patients with rheumatoid arthritis, arteriosclerosis, cardiovascular diseases, HIV infection, nephritis, and neuropathic pain, [19][20][21][22][23][24][25][26][27] it has naturally attracted attention as a potential target of treatment for inflammatory diseases.…”

Coordinated Increase in Serum Platelet-Derived Growth Factor-BB and Transforming Growth Factor-β1 in Patients with Chronic Pancreatitis

“…Serum TGF-β1 is elevated in human subjects with CP [5,27]. Moreover, it has been proposed that serum TGF-β1 may be a useful marker predicting the severity of CP [27].…”