Biomedical subjects

J L Wallace

Publications and source records attributed to J L Wallace.

At least 91 records · Page 5Linked to original sources

PubMed1997

Nonsteroidal anti-inflammatory drug enteropathy in rats: role of permeability, bacteria, and enterohepatic circulation.

BACKGROUND & AIMS: The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID)-induced small intestinal damage remains poorly understood. The aim of this study was to examine the relative importance of the three suggested components of the pathogenesis of NSAID enteropathy, namely, epithelial permeability, enteric bacterial numbers, and enterohepatic recirculation, using an NSAID derivative (nitrofenac) that does not cause small intestinal damage. METHODS: Rats were given diclofenac or nitrofenac at 12-hour intervals. Epithelial permeability to [51Cr]-ethylenediaminetetraacetic acid and enteric bacterial numbers were determined after 1-4 doses of the drugs. Serum levels and biliary excretion of the two drugs were determined by high-performance liquid chromatography. RESULTS: Diclofenac caused a progressive increase in epithelial permeability, marked increases in enteric gram-negative bacterial numbers, and frank intestinal ulceration. Nitrofenac caused similar changes in intestinal permeability after a single dose but no further increase with repeated administration. Moreover, nitrofenac had no effect on enteric bacterial numbers and did not cause frank ulceration. Unlike diclofenac, nitrofenac did not undergo extensive enterohepatic recirculation. Two other NSAIDs that do not undergo enterohepatic recirculation (nabumetone and aspirin) also did not modify enteric bacterial numbers or cause intestinal ulceration. CONCLUSIONS: Enterohepatic recirculation of NSAIDs is of paramount importance in the pathogenesis of enteropathy caused by these drugs, whereas suppression of prostaglandin synthesis is relatively unimportant.

Animals↗

PubMed1997

TNF-alpha facilitates inflammation-induced glucocorticoid secretion in rats with biliary obstruction.

AIMS: We investigated the role of TNF-alpha in inflammation-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis in rats with cholestasis due to bile duct resection. METHODS: Acute inflammation was induced in bile duct or sham resected rats by subcutaneous injection of carrageenan and HPA axis activation was determined by measuring plasma ACTH and corticosterone levels in the absence or presence of TNF-alpha inhibition. RESULTS: Bile duct resected rats had a 2.4-fold elevation in basal circulating TNF-alpha levels compared to sham resected and unoperated controls. Acute inflammation induced by carrageenan injection resulted in a significant increase in plasma ACTH and corticosterone levels in bile duct resected and control rats in the absence of significant changes in plasma TNF-alpha levels. However, bile duct resected rats demonstrated blunted ACTH release coupled with augmented corticosterone secretion in response to carrageenan administration compared to control rats. Inhibition of TNF-alpha activity by pretreating rats with a specific TNF-antiserum or pentoxifylline did not alter inflammation-induced ACTH secretion in bile duct resected or control rats, or corticosterone secretion in control rats. However, anti-TNF treatments significantly attenuated the inflammation-induced rise in plasma corticosterone in bile duct resected rats. CONCLUSIONS: These results indicate that inflammation in rats with biliary obstruction is associated with blunted ACTH release coupled with augmented glucocorticoid secretion facilitated by TNF-alpha. Furthermore, these results suggest that what have been previously considered as low level elevations in circulating TNF-alpha levels can facilitate adrenal glucocorticoid secretion during the inflammatory response.

Adrenocorticotropic Hormone↗

PubMed1997

Aspirin causes rapid up-regulation of cyclo-oxygenase-2 expression in the stomach of rats.

BACKGROUND: Cyclo-oxygenase-1 (COX-1) is believed to produce prostaglandins vital to mucosal defence, whereas cyclo-oxygenase-2 (COX-2) is induced at sites of inflammation. Little is known about the regulation of COX-2 in the stomach, particularly during the period following mucosal injury. In this study, we examined COX-1 and COX-2 expression shortly after administration of NSAIDs or ethanol. METHODS: Fasted rats were given aspirin, salicylate, indomethacin or ethanol (20% or 40%) orally. Three hours later the stomach was excised, the severity of damage scored and samples taken for RT-PCR of COX-1 and COX-2 mRNA and immunohistochemistry. Nitric oxide synthase mRNA (iNOS and eNOS) and activity were also measured. RESULTS: Aspirin, indomethacin and the higher concentration of ethanol produced widespread mucosal damage, whereas salicylate and 20% ethanol caused only superficial epithelial damage. Aspirin caused a significant increase in COX-2 mRNA expression and a marked increase in COX-2 immunoreactivity, particularly in the superficial mucosa. Expression of COX-1 (mRNA and protein) was unaffected by aspirin, as were NOS mRNA expression and enzyme activity. Pre-treatment with prostaglandin E2 prevented the induction of COX-2 by aspirin. Salicylate and indomethacin caused modest increases in COX-2 immunoreactivity but no change in COX-2 mRNA. Neither concentration of ethanol affected COX-2 mRNA or protein expression, suggesting that this was a specific response to the aspirin, rather than to injury. CONCLUSIONS: These results demonstrate a rapid up-regulation of COX-2 expression in response to aspirin, possibly representing a compensatory response to inhibition of gastric prostaglandin synthesis.

Animals↗

PubMed1997

NO-naproxen vs. naproxen: ulcerogenic, analgesic and anti-inflammatory effects.

BACKGROUND: A novel class of nitric oxide-releasing nonsteroidal anti-inflammatory drug (NO-NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gastrointestinal injury than the parent NSAID from which they are derived. The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti-inflammatory properties to the parent NSAID. METHODS: The two drugs were compared in an acute gastric injury model, an antral ulcer model and after twice-daily administration for 18 days (small intestinal damage model). Anti-inflammatory activity was examined in the carrageenan-induced paw oedema model, while analgesia was examined in the acetic acid-induced writhing model. The pharmacokinetic profiles of naproxen vs. NO-naproxen were compared by HPLC analysis. RESULTS: NO-naproxen was found to produce significantly less gastric damage despite inducing similar increases in plasma TNF alpha to naproxen. With chronic administration, small intestinal damage was markedly less with NO-naproxen than with the parent NSAID. However, NO-naproxen exerted superior analgesic and comparable anti-inflammatory effects to naproxen. NO-naproxen was not completely converted to naproxen, but the reduced plasma levels of the latter was not the underlying reason for reduced gastrointestinal toxicity of NO-naproxen. CONCLUSION: NO-naproxen represents a novel, gastrointestinal-sparing NSAID derivative with superior analgesic and comparable anti-inflammatory properties to naproxen.

Analgesics↗

PubMed1997

Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years.

As we approach the 100th year since the introduction of aspirin to the marketplace, the association of gastrointestinal damage with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) remains the major limitation to their use. Although various approaches have been taken to producing NSAIDs with reduced gastrointestinal toxicity, few have significantly reduced the incidence of clinically significant adverse reactions (perforation or hemorrhage). In this review, the mechanisms contributing to the mucosal injury caused by NSAIDs in the stomach, small intestine, and colon are reviewed. In addition, several recent strategies for developing NSAIDs that spare the gastrointestinal tract of injury are discussed. These include selective inhibitors of cyclooxygenase 2, nitric oxide-releasing NSAIDs, and NSAIDs preassociated with zwitterionic phospholipids.

Animals↗

PubMed1997

Underlying mechanisms of portal hypertensive gastropathy.

Gastric mucosal lesions are frequently observed in patients with liver cirrhosis and portal hypertension. Similar lesions can be observed in experimental portal hypertension. This review summarizes our current knowledge of the pathophysiology of portal hypertensive gastropathy, with a particular focus on the microcirculatory disturbances that characterize this condition. The stomach of cirrhotic patients exhibits an increased susceptibility to injury induced by several irritants. Similarly, the stomach of portal hypertensive animals is less resistant to injury. One of the most important factors contributing to the increased susceptibility to damage is an impaired hyperemic response when the epithelium is exposed to irritants. This appears to be related to a reduction in mucosal prostaglandin production and to altered microcirculatory responsiveness to nitric oxide. Nitric oxide overproduction in portal hypertension may have direct effects on gastric blood flow regulation. Elevated production of tumor necrosis factor-alpha by gastric mucosa in portal hypertensive rats has also been shown to contribute to mucosal injury. A better understanding of the pathogenesis of portal hypertensive gastropathy may lead to development of specific therapeutic interventions for this condition.

Animals↗

PubMed1997

Effects of chemical sympathectomy and sensory nerve ablation on experimental colitis in the rat.

We assessed the effects of primary afferent nerve ablation (systemic treatment with capsaicin during adult or neonatal periods), primary afferent nerve activation (intracolonic capsaicin), and sympathectomy [6-hydroxydopamine (6-OHDA)] on the development of colitis induced by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats. We also examined whether lidocaine was effective after ablation of primary afferent nerves or sympathectomy. Colitis was assessed by macroscopic scoring, measurement of myeloperoxidase (MPO) activity, and histology. Systemic capsaicin treatment in adults increased the macroscopic damage score. Capsaicin treatment of neonates did not significantly increase damage score or MPO activity compared with vehicle-treated controls. However, all capsaicin-treated groups had a higher mortality. Intracolonic capsaicin treatment did not alter the severity of colitis. Chemical sympathectomy resulted in a decreased damage score and improved histology compared with controls. In 6-OHDA pretreated rats, lidocaine administration reduced the macroscopic and histological scores and MPO activity almost to control levels. However, lidocaine administration in capsaicin-treated rats attenuated the macroscopic damage but did not improve MPO activity or histology. These data suggest that capsaicin-sensitive nerves play a protective role in experimental colitis and sympathetic nerves contribute to the development of colitis. The beneficial effects of lidocaine appear to be due primarily to its action on enteric nerves.

Administration, Topical↗

PubMed1997

TNF-alpha contributes to the pathogenesis of ethanol-induced gastric damage in cirrhotic rats.

Cirrhotic rats exhibit increased susceptibility to ethanol-induced gastric damage, but the underlying mechanism for this phenomenon remains unclear. Abnormalities of the gastric microcirculation have been reported that may contribute to the increased susceptibility to damage. Decreased gastric synthesis of prostaglandins also likely contributes to impaired mucosal defense in cirrhotic rats. Tumor necrosis factor-alpha (TNF-alpha) has been implicated in mucosal injury, and its synthesis can be inhibited by prostaglandins. Therefore, we hypothesized that TNF-alpha synthesis/ release is altered in cirrhotic rats and plays a role in the pathogenesis of ethanol-induced gastric damage. Cirrhosis was induced by bile duct ligation, whereas controls had sham operations. Topical application of 40% ethanol caused four times as much damage in cirrhotic rats than in controls. Basal plasma TNF-alpha levels did not differ between control and cirrhotic rats, although cirrhotic rats exhibited significantly higher levels of gastric TNF-alpha mRNA. Plasma TNF-alpha increased significantly in control and cirrhotic rats after ethanol administration. Inhibition of TNF-alpha synthesis/release with pentoxifylline, thalidomide, dexamethasone, or immunoneutralization of TNF-alpha (with anti-TNF-alpha) was found to significantly reduce the severity of ethanol-induced gastric mucosal damage in cirrhotic rats. We conclude that TNF-alpha contributes to the pathogenesis of ethanol-induced gastric damage in cirrhotic rats.

Animals↗

PubMed1997

Reduction of shock-induced gastric damage by a nitric oxide-releasing aspirin derivative: role of neutrophils.

The gastric damage associated with hemorrhagic shock appears to occur, at least in part, through neutrophil-dependent mechanisms. Nitric oxide (NO)-releasing derivatives of aspirin have been shown to spare the gastrointestinal tract of injury. As NO can inhibit neutrophil adherence, it is possible that such a derivative of aspirin (NCX-4016) would exert inhibitory effects on neutrophil adherence and therefore be capable of protecting the stomach against shock-induced gastric damage. This hypothesis was tested in this study. Oral administration of NCX-4016 or glyceryl trinitrate or depletion of circulating neutrophils with antineutrophil serum significantly reduced the extent of gastric damage induced by hemorrhagic shock, whereas aspirin had no effect. NCX-4016 and antineutrophil serum pretreatment resulted in significant preservation of gastric blood flow during the shock period. Moreover, NCX-4016, but not aspirin, was capable of inhibiting N-formyl-Met-Leu-Phe-induced leukocyte adherence to postcapillary mesenteric venules. These results suggest that an NO-releasing aspirin derivative reduces the susceptibility of the stomach to shock-induced damage through inhibitory effects on neutrophil adherence to the vascular endothelium.

Animals↗

PubMed1997

Flavonoid-induced gastroprotection in rats: role of blood flow and leukocyte adherence.

To elucidate the mechanisms of flavonoid-induced protection against nonsteroidal anti-inflammatory drug (indomethacin)-induced acute gastric damage, the effects of 5-methoxyflavone and 5-methoxyflavanone on the gastric vasculature were compared both in vivo (using laser Doppler flowmetry in anesthetized rats) and in vitro on rat superior mesenteric arteries. The effects of the compounds on indomethacin-induced leukocyte adherence to mesenteric venules were investigated by intravital videomicroscopy. Oral 5-methoxyflavone reduced indomethacin-induced macroscopic damage by 38 to 99% (ED50 = 5.5 mg/kg). Damage was not significantly reduced by 5-methoxyflavanone. Light microscopy studies also demonstrated a reduction in damage severity. 5-Methoxyflavone, but not 5-methoxyflavanone, increased the gastric conductance significantly. The effects on isolated mesenteric arteries correlated with the effects on in vivo conductance. Finally, indomethacin-induced leukocyte adherence was inhibited to a greater extent by 5-methoxyflavone than by 5-methoxyflavanone. In conclusion, the flavonoid 5-methoxyflavone provides gastroprotection against nonsteroidal anti-inflammatory drug-induced gastric damage. A structurally similar compound, 5-methoxyflavanone, demonstrated minimal gastroprotective activity, suggesting that the double bond of 5-methoxyflavone is required for biological activity. The finding that 5-methoxyflavone (but not 5-methoxyflavanone) significantly increased gastric vascular perfusion and reduced leukocyte adherence to mesenteric venules suggests that these mechanisms may contribute to the flavonoid's gastroprotective activity.

Animals↗

PubMed1997

Nitric oxide-releasing non-steroidal anti-inflammatory drugs: a new generation of antithrombotics?

Long-term use of aspirin as an antithrombotic agent is limited by its toxicity in the gastrointestinal tract. Even very low doses of aspirin can markedly increase the risk of gastrointestinal bleeding and ulceration. Addition of a nitric oxide (NO)-releasing moiety to non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to greatly reduce their ulcerogenic properties as well as their renal toxicity. We proposed that similar derivatisation of aspirin may yield a potent, gastrointestinal-sparing antithrombotic drug. Two prototype compounds (NCX-4215 and NCX-4016; Nicox SA) have been evaluated thus far. Each shows comparable or better anti-aggregatory activity to aspirin while not inducing detectable gastric damage. Current studies are aimed at determining what the optimal balance is between nitric oxide release and inhibition of thromboxane synthesis to achieve good antithrombotic activity with low toxicity. NO-aspirin derivatives appear to offer great potential as gastrointestinal-sparing antithrombotic drugs.

Journal Article↗

PubMed1997

Inflammatory mediators in gastrointestinal defense and injury.

Irrespective of where ulceration occurs in the gastrointestinal tract, it is almost always associated with mucosal inflammation. The chemical mediators that coordinate inflammatory responses also have the capability to alter the resistance of the mucosa to injury. Some inflammatory mediators increase the resistance of the mucosa to injury, while others exert "ulcerogenic" effects. In this review, we provide an overview of the major inflammatory mediators that have been shown to exert effects on mucosal defense in the gastrointestinal tract. Among the inflammatory mediators discussed are the eicosanoids (prostaglandins, leukotrienes, thromboxanes), nitric oxide, neuropeptides, and cytokines (IL-1beta, TNF alpha). Several of these mediators are considered potential therapeutic targets for the treatment of ulcerative diseases of the digestive system, and, in some cases, clinical data are available on the efficacy of such approaches.

Animals↗

PubMed1996

Exacerbation of inflammation-associated colonic injury in rat through inhibition of cyclooxygenase-2.

Cyclooxygenase type 1 is constitutively expressed and accounts for synthesis of prostaglandins in the normal gastrointestinal tract. Cyclooxygenase-2 is expressed at sites of inflammation. Selective inhibitors of cyclooxygenase-2 have been suggested to spare gastrointestinal prostaglandin synthesis, and therefore lack the ulcerogenic effects associated with standard nonsteroidal antiinflammatory drugs. However, the effects of cyclooxygenase-2 inhibitors on inflamed gastrointestinal mucosa have not been examined. We examined cyclooxygenase-2 mRNA and protein expression before and after induction of colitis in the rat, the contribution of cyclooxygenase-2 to colonic prostaglandin synthesis during colitis and the effects of selective inhibitors of cyclooxygenase-2 on colonic injury in this model. Cyclooxygenase-2 mRNA expression increased three to sixfold during the period 24 h to 1 wk after induction of colitis, with marked increases in cyclooxygenase-2 protein expression in the lamina propria and muscularis of the colon during colitis. Cyclooxygenase-1 expression (mRNA and protein) was not affected by the induction of colitis. The prostaglandins produced during colitis were largely derived from cyclooxygenase-2. Treatment with selective cyclooxygenase-2 inhibitors resulted in exacerbation of colitis, with perforation occurring when the compounds were administered for a week. These studies demonstrate that suppression of cyclooxygenase-2 can result in exacerbation of inflammation-associated colonic injury.

Animals↗

PubMed1996

Prostaglandins modulate the responsiveness of the gastric microcirculation of sodium nitroprusside in cirrhotic rats.

Cirrhotic rats have an increased susceptibility to ethanol-induced gastric injury, related to an inability to mount a defensive gastric hyperemic response to luminal irritants, and associated with an impaired reactivity of the gastric microcirculation to nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)-dependent vasodilators. Whether this hyporesponsiveness is in some way related to depressed prostaglandin synthesis by the stomach of cirrhotic rats is not clear. The aims of this study were to evaluate the role of NO and prostaglandins in the regulation of the gastric microcirculation under resting conditions and in response to administration of sodium nitroprusside, as well as to investigate the mechanisms of the hyporesponsiveness of the gastric microcirculation to nitrovasodilators. Cirrhosis was induced in rats by bile duct ligation, and controls had sham-operation. NG-nitro-L-arginine-methyl-ester (L-NAME) and indomethacin administration produced a greater reduction in gastric blood flow in cirrhotic rats than controls. Indomethacin pretreatment almost completely abolished the responsiveness to sodium nitroprusside (NaNP) in cirrhotic rats, while not affecting controls. Long-term administration of misoprostol to cirrhotic rats restored to normal the responsiveness to NaNP, whereas long-term administration of aspirin to healthy rats resulted in a hyporesponsiveness of the gastric microcirculation to NaNP similar to that seen in cirrhotic rats. We conclude that there are interactions between NO and prostaglandins in regulating gastric blood flow in both healthy and cirrhotic rats. The hyporesponsiveness of the gastric microcirculation of cirrhotic rats to a nitrovasodilator may occur as a consequence of prolonged depression of gastric prostaglandin synthesis.

Analysis of Variance↗

PubMed1996

Hepatic mucosal mast cell hyperplasia in rats with secondary biliary cirrhosis.

Mast cells have been shown to play a role in many chronic inflammatory and fibrotic disorders. However, their possible contribution to the pathological changes that occur in liver cirrhosis is unknown. To explore this, we examined whether changes in hepatic mast cell number and mediator content were associated with fibrotic changes in experimental biliary cirrhosis. Rats were studied 7, 14, or 21 days after bile duct resection (BDR). Hepatic mast cells were identified by histochemical and immunohistochemical stains. Rat mast cell protease II (RMCP-II), a marker of mast cell degranulation, was measured in liver by enzyme-linked immunosorbent assay. Hepatic collagen deposition was assessed by Sirius Red F3BA staining. In day 21 BDR rats, there was a one- to twofold increase (P < .001) in the number of hepatic mast cells, but this was not observed in day 7 or 14 BDR rats. Mild fibrotic changes were noted in BDR rat livers as early as 7 days after induction of cholestasis. Significant expansion and organization of fibrous tissue had occurred in day 14 BDR rats which progressed to bridging fibrosis by day 21. Liver RMCP-II levels were decreased by 50 percent (P < .05) and mast cell degranulation was apparent as shown by histamine immunostaining. These results suggest that hepatic mast cell hyperplasia and degranulation occur during prolonged cholestasis in the rat. Although these changes do not correlate with the onset of hepatic fibrosis, they do occur at a time during which there is significant deposition and organization extracellular matrix elements. Hepatic mast cells, by releasing profibrogenic mediators, may contribute to fibrotic changes in biliary cirrhosis.

Animals↗

PubMed1996

Long-term antigen challenge results in progressively diminished mucosal mast cell degranulation in rats.

BACKGROUND & AIMS: The effects of short-term antigenic activation of mast cells on the gastrointestinal tract have been well characterized, but little is known about the effects of long-term exposure to antigen on mucosal mast cell reactivity. The aim of this study was to determine the effects of long-term antigen exposure on mucosal mast cell reactivity in the gastrointestinal mucosa. METHODS: Rats sensitized to chicken ovalbumin were orally challenged (short-term or long-term) with antigen. Rat mast cell protease II (RMCP-II) content was measured in serum as an index of mucosal mast cell degranulation. RESULTS: Short-term oral antigen challenge caused a 30-fold increase in serum RMCP-II levels. RMCP-II release was markedly diminished in long term-challenged rats (P < 0.001), despite increased tissue RMCP-II levels in stomach and jejunum. Although short-term antigen challenge significantly increased gastric acid secretion, no such response was observed after the long-term antigen challenge. In rats undergoing long-term challenge, a significant release of RMCP-II in response to intravenous antigen was not observed; however, mucosal mast cells remained responsive to intravenous anti-immunoglobulin E. CONCLUSIONS: Repeated activation of mucosal mast cells results in a progressive diminution of RMCP-II release not attributable to depletion of this mediator. This may represent an adaptive response aimed at minimizing the potentially deleterious effects of repeated exposure to an antigen.

Animals↗

PubMed1996

Mast cells do not contribute to nonsteroidal anti-inflammatory drug-induced gastric mucosal injury in rodents.

BACKGROUND: By releasing pro-ulcerogenic mediators, mast cells may contribute to the mucosal injury associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS: To study this, rat and mouse models of NSAID-induced gastric damage were used in which administration of indomethacin causes haemorrhagic injury in the corpus region of the stomach, and the "re-feeding" model in which penetrating antral ulcers are induced in the rat by naproxen. Mast cell degranulation was determined histologically and by measurement of tissue and serum levels of rat mast cell protease-II, a mediator specific to mucosal mast cells. The effects of either increasing or decreasing the number of gastric mucosal mast cells on the susceptibility of the stomach to injury induced by indomethacin were also studied. RESULTS: Gastric injury induced by indomethacin was not accompanied by significant mast cell degranulation. Moreover, neither increasing nor decreasing the number of gastric mucosal mast cells had a significant effect on the susceptibility of the gastric mucosa to damage induced by indomethacin. In the re-feeding model, prior depletion of gastric mucosal mast cells did not significantly affect the severity of antral ulceration induced by naproxen, nor the ability of prostaglandin E2 to prevent this damage. Finally, indomethacin-induced damage was similar in severity in mice with a genetic defect resulting in the complete absence of mast cells as it was in normal, congenic littermates. CONCLUSION: Mast cells do not play a significant role in the development of gastric injury induced by acute NSAID administration in the rat or mouse.

Animals↗

PubMed1996

The cellular and molecular basis of gastric mucosal defense.

The association between colonization of the stomach by Helicobacter pylori and peptic ulcer disease has stimulated a renewal of interest in the factors that render the gastric mucosa resistant to injury induced by endogenous secretions and ingested toxins. Mucosal defense consists of a complex network of components that function in concert with one another. This network includes: 1) the extramucosal components such as acid, mucus, surface-active phospholipids, and bicarbonate; 2) the epithelium itself; 3) the microcirculation and sensory afferent neurons beneath the epithelium; 4) the mucosal immune system; and 5) the ability of the mucosa to undergo repair. In the past two decades, an enormous amount has been learned about the cellular and molecular basis of the various components of mucosal defense, including a better understanding of the chemical substances that coordinate mucosal responses to injury. In this paper, we review the factors that contribute to mucosal defense, the cellular and molecular mechanisms through which mucosal defense is modulated, and the chemical mediators that play key roles in this process.

Animals↗