Bacterial Endotoxin: A Trigger Factor for Alcoholic Pancreatitis? Evidence From a Novel, Physiologically Relevant Animal Model

Vonlaufen, Alain; Xu, Zhijian; Daniel, Balu; Kumar, Rakesh K.; Pirola, Romano C.; Wilson, Jeremy S.; Apte, Minoti V.

doi:10.1053/j.gastro.2007.06.062

Cited by 133 publications

(135 citation statements)

References 39 publications

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“…The importance of this mechanism in ALD has been impressively documented by Uesugi and colleagues (2001) and is further supported by the finding of TLR-4 gene polymorphisms connected to liver fibrosis (Guo et al, 2009;Huang et al, 2007). Similarly, development of chronic pancreatitis was enhanced in the alcohol-fed rats with repeated injections of LPS as evidenced by acinar atrophy and pancreatic fibrosis (Vonlaufen et al, 2007) (Fig. 2A).…”

Section: Lps-mediated Alcohol-induced Tissue Injurysupporting

confidence: 62%

Alcohol, Signaling, and ECM Turnover

Seth

El-Guindy

Apte

et al. 2009

Alcoholism Clin & Exp Res

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Alcohol is recognized as a direct hepatotoxin, but the precise molecular pathways that are important for the initiation and progression of alcohol-induced tissue injury are not completely understood. The current understanding of alcohol toxicity to organs suggests that alcohol initiates injury by generation of oxidative and nonoxidative ethanol metabolites and via translocation of gut-derived endotoxin. These processes lead to cellular injury and stimulation of the inflammatory responses mediated through a variety of molecules. With continuing alcohol abuse, the injury progresses through impairment of tissue regeneration and extracellular matrix (ECM) turnover, leading to fibrogenesis and cirrhosis. Several cell types are involved in this process, the predominant being stellate cells, macrophages, and parenchymal cells. In response to alcohol, growth factors and cytokines activate many signaling cascades that regulate fibrogenesis. This mini-review brings together research focusing on the underlying mechanisms of alcohol-mediated injury in a number of organs. It highlights the various processes and molecules that are likely involved in inflammation, immune modulation, susceptibility to infection, ECM turnover and fibrogenesis in the liver, pancreas, and lung triggered by alcohol abuse.

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Section: Lps-mediated Alcohol-induced Tissue Injurysupporting

confidence: 62%

Alcohol, Signaling, and ECM Turnover

Seth

El-Guindy

Apte

et al. 2009

Alcoholism Clin & Exp Res

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“…Experiments were conducted in LPS-treated adult male rats (n ϭ 10 -12/group for hormonal studies). A protocol of three consecutive injections of LPS (250 g/kg ip) at 24-h intervals was implemented, as adapted from previous studies, to induce standard acute immune/inflammatory responses in the experimental animals (19,26,27,34,38). Male rats injected with vehicle (saline 0.9%; n ϭ 10) were used as controls.…”

Section: Animals and Reagentsmentioning

confidence: 99%

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

Castellano

Bentsen

Martín‐Romero

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Tena-Sempere M. Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects. Am J Physiol Endocrinol Metab 299: E54 -E61, 2010. First published April 20, 2010 doi:10.1152/ajpendo.00081.2010.-Severe inflammatory challenges are frequently coupled to decreased food intake and disruption of reproductive function, the latter via deregulation of different signaling pathways that impinge onto GnRH neurons. Recently, the hypothalamic Kiss1 system, a major gatekeeper of GnRH function, was suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern of hypothalamic kisspeptin immunoreactivity (IR) and hormonal responses to kisspeptin during the acute inflammatory phase. LPS injections induced a dramatic but transient drop of serum LH and testosterone levels. Suppression of gonadotropic function was associated with a significant decrease in kisspeptin-IR in the arcuate nucleus (ARC) that was not observed under conditions of metabolic stress induced by 48-h fasting. In addition, absolute responses to kisspeptin-10 (Kp-10), in terms of LH and testosterone secretion, were significantly attenuated in LPS-treated males that also displayed a decrease in food intake and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key center for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation.Kiss1/kisspeptins; gonadotropin-releasing hormone; gonadotropins; lipopolysaccharide S IMMUNE/INFLAMMATORY CHALLENGES, such as those associated with severe bacterial infections, are commonly coupled with transient suppression of dispensable functions for individual survival, such as reproduction. Among a plethora of biological responses, administration of lipopolysaccharide S (LPS), a glycolipid of gram-negative bacteria, has been shown to disrupt puberty onset and gonadotropic function through deregulation of an array of signaling pathways, including different proinflammatory cytokines (IL-1, IL-6, TNF␣), growth factors, neurotransmitters (catecholamines, ␥-aminobutyric acid), and neuropeptides (corticotropin-releasing factor, arginine vasopressin, opioids) (1,10,16,28,33,35,37,39). However, although compelling evidence suggests that the above factors are variably involved in the suppression of the gonadotropinreleasing hormone (GnRH)/LH system by bacterial endotoxin (37,...

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“…Some studies have indicated that when severe acute pancreatitis is stimulated by LPS, the expressions of cytokines and cell adhesion molecules are significantly up-regulated in pancreas, thereby promoting the accumulation of excessive neutrophils in inflammatory region and leading to the injury of pancreas and other organs [154,155]. Although it has been known that the translocation of intestinal bacteria and endotoxins is a key to secondary bacterial infection in necrotic pancreatic tissue, the mechanism of how multiple organ failure develops during pancreatitis has not yet been fully clarified [156].…”

Section: Toll-like Receptor-4 (Tlr4)mentioning

confidence: 99%

Microcirculatory Disturbances in the Pathogenesis of Acute Pancreatitis

Uhlmann¹

2012

Acute Pancreatitis

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Bacterial Endotoxin: A Trigger Factor for Alcoholic Pancreatitis? Evidence From a Novel, Physiologically Relevant Animal Model

Cited by 133 publications

References 39 publications

Alcohol, Signaling, and ECM Turnover

Alcohol, Signaling, and ECM Turnover

Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

Microcirculatory Disturbances in the Pathogenesis of Acute Pancreatitis

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