Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis.

Crofford, Leslie J.; Sano, Hajime; Karalis, Katia; Webster, Elizabeth; Goldmuntz, Ellen A.; Chrousos, George P.; Wilder, Ronald L.

doi:10.1172/jci116150

Cited by 196 publications

(108 citation statements)

References 55 publications

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“…[ 32 P]dCTP (0.25 l) (3,000 Ci͞mmol, New England Nuclear) was added to the reaction mixture to radiolabel the products of the amplification reaction. The temperature profile for the RT-amplification reaction and the sequence for SP primers were as previously reported by Crofford et al (36). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) primers, used as an internal standard, were purchased from CLONTECH.…”

Section: Materials [mentioning

confidence: 99%

“…PCR of reverse transcribed cDNA was performed as described using specific primers for SP͞PPT (40 cycles) or GAPDH (25 cycles). The PCR primers for SP͞preprotachykinin were designed to detect the ␣, ␤, and ␥ forms of the PPT mRNA (36). [ 32 P]-labeled PCR products were electrophoresed on 3.5 or 5% native polyacrylamide gels (depending on the size of the product), and autoradiograms were obtained.…”

Section: Effect Of Sp-antagonist On Toxin A-induced Tnf␣ Release Frommentioning

confidence: 99%

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Increased substance P responses in dorsal root ganglia and intestinal macrophages duringClostridium difficiletoxin A enteritis in rats

Castagliuolo

Keates

Qiu

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

155

124

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Previously we reported that pretreatment of rats with the substance P (SP) antagonist CP-96,345 inhibits the enterotoxic responses following administration of toxin A from Clostridium difficile into ileal loops, indicating that SP participates in the intestinal responses to this toxin. We now report that injection of toxin A into rat ileum causes a rapid increase in SP content in lumbar dorsal root ganglia (DRG) and mucosal scrapings 30-60 min after toxin A administration. Toxin A-mediated f luid secretion, mannitol permeability, and ileal histologic damage is significantly increased only after 2 hr. Toxin A also causes an increase in the abundance of SP mRNA in lumbar DRG and ileal mucosa as measured by reverse transcription-PCR. Lamina propria macrophages (LPMs) obtained from toxin A-injected loops release greater amounts of tumor necrosis factor ␣ (TNF␣) and SP as compared with LPMs isolated from buffer-injected loops (P < 0.01). Pretreatment of rats with the SP antagonist CP-96,345 inhibits toxin A-mediated TNF␣ release from isolated LPMs, whereas an inactive enantiomer (CP-96,344) of the SP antagonist has no effect. LPMs obtained from toxin A-injected ileal loops incubated in vitro with SP (10 ؊8 to 10 ؊9 M) show enhanced TNF␣ secretion, whereas LPMs isolated from buffer-injected loops do not respond to SP. In addition, LPMs obtained from toxin A-injected ileal loops incubated in vitro with CP-96,345 showed a diminished TNF␣ release. Our results indicate that activated LPMs secrete SP during toxin A enteritis that can lead to secretion of cytokines, suggesting an autocrine͞paracrine regulation of cytokine secretion by SP from LPMs during intestinal inf lammation.Substance P (SP), an 11-aa peptide member of the tachykinin family originally isolated by Chang and Leeman (1), is a peptide distributed throughout the central and peripheral nervous system. In the intestine, SP has been found in capsaicin-sensitive sensory neurons (2), enteric neurons (3), as well as intestinal enteroendocrine cells (4). SP is also synthesized in the cell bodies of the dorsal root ganglia (DRG) (5), and evidence indicates that release of SP from DRG to spinal cord mediates nociceptive and inflammatory stimuli (6-8). Recently, Reinshagen et al. (9) reported decreased levels of SP in the DRG of rabbits 48 hr after induction of colitis, suggesting that SP may be released from sensory neurons during the acute phase of inflammation. However, there are no studies specifically evaluating the SP content in the DRG during acute intestinal inflammation mediated by bacterial enterotoxins.In addition to its role as a neurotransmitter, SP also participates in immune and inflammatory responses. Mast cells (10), polymorphonuclear leukocytes (11), T lymphocytes (12, 13), and macrophages (14) can respond to SP, indicating that the effects of SP during inflammation may be mediated by direct activation of these cells. SP levels are also elevated in inflamed tissues (15-17), and increased binding sites for SP have been demonstrated at sites o...

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Section: Materials [mentioning

confidence: 99%

Section: Effect Of Sp-antagonist On Toxin A-induced Tnf␣ Release Frommentioning

confidence: 99%

Increased substance P responses in dorsal root ganglia and intestinal macrophages duringClostridium difficiletoxin A enteritis in rats

Castagliuolo

Keates

Qiu

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

155

124

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“…CRH plays a dual role in the pathophysiology of inflammation. CRH secreted from the hypothalamus has indirect antiinflammatory effects via stimulation of glucocorticoid release, but CRH is also expressed peripherally, and its expression is increased in leukocytes, nerve fibers, and other cells involved in inflammatory reactions (7)(8)(9)(10)(11)(12). Moreover, in vivo and in vitro studies indicate that CRH is a potent proinflammatory peptide (7,(12)(13)(14)(15).…”

mentioning

confidence: 99%

Corticotropin-releasing hormone (CRH) requirement inClostridium difficiletoxin A-mediated intestinal inflammation

Anton

Mykoniatis²,

Pan³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

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Clostridium difficile, the causative agent of antibiotic-associated colitis, mediates inflammatory diarrhea by releasing toxin A, a potent 308-kDa enterotoxin. Toxin A-induced inflammatory diarrhea involves many steps, including mucosal release of substance P (SP) corticotropin-releasing hormone (CRH) and neutrophil transmigration. Here we demonstrate that, compared with wild type, mice genetically deficient in CRH (Crh ؊/؊ ) have dramatically reduced ileal fluid secretion, epithelial cell damage, and neutrophil transmigration 4 h after intraluminal toxin A administration. This response is associated with diminished mucosal activity of the neutrophil enzyme myeloperoxidase compared with that of wildtype mice. In wild-type mice, toxin A stimulates an increase in intestinal SP content compared with buffer administration. In contrast, toxin A administration in Crh ؊/؊ mice fails to result in an increased SP content. Moreover, immunohistochemical experiments showed that CRH and SP are colocalized in some enteric nerves of wild-type mice, and this colocalization is more evident after toxin A administration. These results provide direct evidence for a major proinflammatory role for CRH in the pathophysiology of enterotoxin-mediated inflammatory diarrhea and indicate a SP-linked pathway.C orticotropin-releasing hormone (CRH), a 41-aa peptide, is a major peptide hormone that modulates the activity of the hypothalamic-pituitary-adrenal axis during stress, including inflammation (1-3). CRH mediates its effects by binding to its G protein-coupled receptor subtypes, CRH1 and CRH2 (4-6). CRH plays a dual role in the pathophysiology of inflammation. CRH secreted from the hypothalamus has indirect antiinflammatory effects via stimulation of glucocorticoid release, but CRH is also expressed peripherally, and its expression is increased in leukocytes, nerve fibers, and other cells involved in inflammatory reactions (7-12). Moreover, in vivo and in vitro studies indicate that CRH is a potent proinflammatory peptide (7,(12)(13)(14)(15).A limited number of studies indicate that CRH and its receptors play a role in the pathophysiology of intestinal inflammation. Thus, Van Tol et al. (11) found increased CRH expression in the rat cecum in colitis induced by injection of peptidoglycan-polysaccharide polymers. Increased expression of CRH-immunoreactive cells was also evident in the colonic mucosa of patients with inflammatory bowel disease (16). CRH gene expression is increased in hypothalamic neurons during colitis after intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (17) and appears to play a protective role in the worsening of experimental colitis induced by stress (18). We have recently shown that expression of CRH as well as CRH1 and CRH2 was dramatically increased in mouse ileum shortly after intraluminal administration of Clostridium difficile toxin A (19). Moreover, experiments with CRH receptor antagonists indicate that CRH plays a proinflammatory role in toxin A-induced intestinal secretion and inflammatio...

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“…Rat b-Actin was amplified using primers described ics, Sunnyvale, CA). ERK kinase assays were performed as described elsewhere 50 in a 50-mL PCR reaction containing 1 mmol/L MgCl 2 , previously. 40 Briefly, 25 mg of liver nuclear extract was incubated 50 mmol/L KCl, and 10 mmol/L Tris (pH 8.3) and using 1 mL of with anti-ERK-2 antibody (C-14, Santa Cruz Biotechnology, Santa complementary DNA template.…”

mentioning

confidence: 99%

Reperfusion after liver transplantation in rats differentially activates the mitogen-activated protein kinases

et al. 1997

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storage before transplantation correlates clinically with inThe injury resulting from cold ischemia and warm recreased primary graft nonfunction, graft rejection, and rate perfusion during liver transplantation is a major clinical of re-transplantation. 4,5 problem that limits graft success. Kupffer cell activation Reperfusion injury is difficult to study clinically, but has plays a pivotal role in reperfusion injury, and Kupffer been investigated in animal models, including orthotopic cell products, including free radicals and tumor necrosis liver transplantation in rats. These studies have shown that factor a (TNF-a), are implicated as damaging agents.hepatic reperfusion following ischemia induces Kupffer cell However, the second messengers and signaling pathactivation, superoxide formation, and elevated plasma levels ways that are activated by the stress of hepatic ischemia/ of tumor necrosis factor a (TNF-a). 6,7 Pretreatment with reperfusion remain unknown. The purpose of this study methyl palmitate inhibits Kupffer cell activation and imis to assess the activation of the three known vertebrate mitogen activated protein kinase (MAPKs) and the acti-proves transplant survival threefold, thereby supporting a vating protein 1 (AP-1) transcription factor in response role for Kupffer cells in reperfusion injury. 8 In addition, treatto ischemia and reperfusion in the transplanted rat ment with agents that suppress TNF-a release from activated liver. There was a potent, sustained induction of c-jun Kupffer cells decrease transplant failure.9 Nisoldipine, a Ca 2/ N-terminal kinase (JNK), but not of the related MAPKs channel blocker, reduces plasma levels of TNF-a and inextracellular signal-regulated kinases (ERK) or p38, creases transplant survival time. 10,11 Similarly, pentoxifylupon reperfusion after transplantation. TNF-a messen-line, a methylxanthine which suppresses TNF-a messenger ger RNA (mRNA) levels and transcription factors AP-1 RNA (mRNA) accumulation in response to lipopolysacchaand nuclear factor-kB (NF-kB) were induced in the liver ride, has a protective effect on liver grafts.12 Taken together, after 60 minutes of reperfusion. Finally, there was an these data suggest an important role for TNF-a in mediating elevation of ceramide, but not diacylglycerol or sphingo-reperfusion injury. sine, in the transplanted liver. Ceramide is a second mes-TNF-a is a pleiotropic cytokine that induces cellular effects senger generated by TNF-a treatment and is an activator ranging from proliferation to apoptosis. TNF-a is a potent of JNK. Because JNK activation preceded the elevations activator of activating protein 1 (AP-1) and NF-kB transcripin ceramide and TNF-a mRNA, these results suggest that tion factors and of the c-jun N-terminal kinase (JNK, also increased hepatic TNF-a and ceramide may perpetuate known as stress-activated protein kinase, SAPK).13-15 JNK is JNK induction, but that they are not the initiating sig-a member of the vertebrate mitogen activated protein kinase nals of JNK activation during reperfus...

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Local secretion of corticotropin-releasing hormone in the joints of Lewis rats with inflammatory arthritis.

Cited by 196 publications

References 55 publications

Increased substance P responses in dorsal root ganglia and intestinal macrophages duringClostridium difficiletoxin A enteritis in rats

Increased substance P responses in dorsal root ganglia and intestinal macrophages duringClostridium difficiletoxin A enteritis in rats

Corticotropin-releasing hormone (CRH) requirement inClostridium difficiletoxin A-mediated intestinal inflammation

Reperfusion after liver transplantation in rats differentially activates the mitogen-activated protein kinases

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