CGRP in the Serum of Endotoxin-Treated Rats Suppresses Lymphoproliferation

Wang, X.; Fiscus, Ronald R.; Tang, Zan-Mei; Yang, Lihua; Wu, Jianxin; Fan, Shujun; Mathews, Herbert L.

doi:10.1006/brbi.1994.1027

Cited by 30 publications

(16 citation statements)

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“…The concentration of a-CGRP and b-CGRP (10 À9 M) used to stimulate purified mouse BDL cholangiocytes was in the range of that used in other in vitro studies 33,34 and was similar to the circulating levels (pM range) of CGRP found in humans, 35 rats, 34 and mice in present studies (Table 1). Following isolation, cholangiocytes were incubated at 371C for 1 h to regenerate membrane proteins damaged by proteolytic treatment.…”

Section: Intracellular Signaling Mechanismssupporting

confidence: 82%

Knockout of α-calcitonin gene-related peptide reduces cholangiocyte proliferation in bile duct ligated mice

Glaser

Ueno

DeMorrow

et al. 2007

Laboratory Investigation

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The role of sensory innervation in the regulation of liver physiology and the pathogenesis of cholestatic liver disease are undefined. Biliary proliferation has been shown to be coordinately controlled by parasympathetic and sympathetic innervation of the liver. The aim of our study was to address the role of the sensory neuropeptide calcitonin gene-related peptide (a-CGRP) in the regulation of cholangiocyte proliferation during cholestasis induced by extrahepatic bile duct obstruction (BDL). Our study utilized a knockout (KO) mouse model, which lacks the sensory neuropeptide a-CGRP. Wildtype (WT) and a-CGRP KO mice were subjected to sham surgery or BDL for 3 and 7 days. In addition, immediately after BDL, WT and KO mice were administered the CGRP receptor antagonist (CGRP 8-37 ) for 3 and 7 days by osmotic minipumps. Liver sections and isolated cholangiocytes were evaluated for proliferation markers. Isolated WT BDL (3 days) cholangiocytes were stimulated with a-and b-CGRP and evaluated for proliferation and cAMP-mediated signaling. Lack of a-CGRP inhibits cholangiocyte proliferation induced by BDL at both 3 and 7 days. BDL-induced cholangiocyte proliferation in WT mice was associated with increases of circulating a-CGRP levels. In vitro, a-and b-CGRP stimulated proliferation in purified BDL cholangiocytes, induced elevation of cAMP levels, and stimulated the activation of cAMPdependent protein kinase A and cAMP response element binding protein DNA binding. In conclusion, sensory innervation of the liver and biliary expression of a-CGRP play an important role in the regulation of cholangiocyte proliferation during cholestasis.

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Section: Intracellular Signaling Mechanismssupporting

confidence: 82%

Knockout of α-calcitonin gene-related peptide reduces cholangiocyte proliferation in bile duct ligated mice

Glaser

Ueno

DeMorrow

et al. 2007

Laboratory Investigation

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“…Huttemeier et al (1993) have reported that a CGRP receptor antagonist, hCGRP8-37 was used to block selectively the cardiovascular actions of endogenous CGRP during the development of endotoxin shock. Their data, coupled with previous reports from our and other laboratories, showing that the hCGRP8-37 is an effective blocker of both vasodilatation and immunosuppression caused by CGRP (Han et al, 1990b;Wang et al, 1994;1995a), have provided direct evidence that CGRP contributes significantly to the hypotension, tachycardia and immunosuppression during endotoxin shock. The question remaining is whether endotoxin can directly trigger the release of CGRP from perivascular nerves.…”

Section: Resultssupporting

confidence: 60%

Rapid nitric oxide‐ and prostaglandin‐dependent release of calcitonin gene‐related peptide (CGRP) triggered by endotoxin in rat mesenteric arterial bed

Wang¹,

Wu²,

Tang³

et al. 1996

British J Pharmacology

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1 Our objective was to determine whether endotoxin (ETX) could directly trigger the release of calcitonin gene-related peptide (CGRP) from perivascular sensory nerves in the isolated mesenteric arterial bed (MAB) of the rat and to determine whether nitric oxide (NO) and prostaglandins (PGs) are involved. 2 ETX caused time-and concentration-dependent release of CGRP, and as much as a 17 fold increase in CGRP levels in the perfusate at 10-15 min after the administration of ETX (50 ,ug ml-'). 3 CGRP-like immunoreactivity in the perfusate was shown to co-elute with synthetic rat CGRP by reverse-phase h.p.l.c. 4 Pretreatment of MAB with capsaicin or ruthenium red inhibited ETX-induced CGRP release by 90% and 71%, respectively. ETX-evoked CGRP release was decreased by 84% during Ca2"-free perfusion.5 The release of CGRP evoked by ETX was enhanced by L-arginine by 43% and inhibited by Nwnitro-L-arginine (L-NOARG) and methylene blue by 37% and 38%, respectively. L-Arginine reversed the effect of L-NOARG. 6 Indomethacin and ibuprofen also inhibited the ETX-induced CGRP release by 34% and 44%, respectively. No additive inhibition could be found when L-NOARG and indomethacin were concomitantly incubated. 7 The data suggest that ETX triggers the release of CGRP from capsaicin-sensitive sensory nerves innervating blood vessels. The ETX-induced CGRP release is dependent on extracellular Ca2" influx and involves a ruthenium red-sensitive mechanism. Both NO and PGs appear to be involved in the ETXinduced release of CGRP in the rat mesenteric arterial bed.

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“…It was reported that CGRP could suppress lymphoproliferation induced by Con A (14,15). This study proved that T lymphocyte mitogens could promote ␤-CGRP synthesis and secretion by lymphoid cells.…”

Section: Effect Of Lymphocyte-derived Cgrp On Rat Thymocyte Proliferasupporting

confidence: 62%

“…CGRP inhibits the proliferation of T lymphocytes (14,15) and the production of cytokines, such as IL-2, IFN-␥, and TNF-␣ in T lymphocytes (16), and also inhibits the killing function of NK cells and IL-2-activated lymphocytes (24,25). CGRP may be involved in thymocyte development by inducing apoptosis of thymocytes via CGRP-specific receptors (26).…”

Section: Discussionmentioning

confidence: 99%

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Induction and Expression of β-Calcitonin Gene-Related Peptide in Rat T Lymphocytes and Its Significance

Xing¹,

Guo²,

Wang³

2000

The Journal of Immunology

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Our previous data have shown that rat lymphocytes can synthesize calcitonin gene-related peptide (CGRP), a neuropeptide. In this study the type, characteristics, and functional role of lymphocyte-derived CGRP were investigated. The results showed that treatment with Con A (4 μg/ml) and recombinant human IL-2 (rhIL-2; 750 U/ml) for 3–5 days induced CGRP synthesis and secretion by lymphocytes from both thymus and mesenteric lymph nodes in a time-dependent manner. Stimulation of these cells with Con A (1–8 μg/ml) or rhIL-2 (94–1500 U/ml) for 5 days induced a significant increase in CGRP secretion in a concentration-dependent manner. The maximal secretion of CGRP with Con A by thymocytes was elevated from 104 ± 11 to 381 ± 44 pg/108 cells, and that by mesenteric lymph node lymphocytes was elevated from 83 ± 10 to 349 ± 25 pg/108 cells, respectively. The maximal CGRP secretion with rhIL-2 by thymocytes was elevated from 116 ± 3 to 607 ± 23 pg/108, and that by mesenteric lymph node lymphocytes was elevated from 117 ± 9 to 704 ± 37 pg/108 cells, respectively. The nucleotide sequencing study showed that lymphoid cells expressed β-CGRP cDNA only. The levels of β-CGRP mRNA in mitogen-stimulated lymphocytes of both sources were also increased. However, LPS had no such effect on either source of cells. hCGRP8–37 (2.0 μM), a CGRP1 receptor antagonist, enhanced Con A-induced proliferation and IL-2 release of thymocytes by 41.3 and 35.8% over those induced by Con A alone, respectively. The data suggest that T lymphocyte mitogens can induce the production of endogenous β-CGRP from T lymphocytes, which may partially inhibit the proliferation and IL-2 release of rat T lymphocyte under immune challenges.

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CGRP in the Serum of Endotoxin-Treated Rats Suppresses Lymphoproliferation

Cited by 30 publications

References 0 publications

Knockout of α-calcitonin gene-related peptide reduces cholangiocyte proliferation in bile duct ligated mice

Knockout of α-calcitonin gene-related peptide reduces cholangiocyte proliferation in bile duct ligated mice

Rapid nitric oxide‐ and prostaglandin‐dependent release of calcitonin gene‐related peptide (CGRP) triggered by endotoxin in rat mesenteric arterial bed

Induction and Expression of β-Calcitonin Gene-Related Peptide in Rat T Lymphocytes and Its Significance

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