scholarly journals Pituitary Adenylate Cyclase-Activating Polypeptide Alleviates Intestinal, Extra-Intestinal and Systemic Inflammatory Responses during Acute Campylobacter jejuni-induced Enterocolitis in Mice

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 805
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Campylobacter Jejuni ◽  
Post Infection ◽  
Inflammatory Responses ◽  
Clinical Signs ◽  
Systemic Circulation ◽  
Cell Responses ◽  
Pituitary Adenylate Cyclase ◽  
Gastrointestinal Colonization ◽  
First Time

Human Campylobacter jejuni infections are emerging, and constitute a significant health burden worldwide. The ubiquitously expressed pituitary adenylate cyclase-activating polypeptide (PACAP) is well-known for its cell-protective and immunomodulatory effects. In our actual intervention study, we used an acute campylobacteriosis model and assessed the potential disease-alleviating effects of exogenous PACAP. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and treated with synthetic PACAP38 intraperitoneally from day 2 until day 5 post-infection. Whereas PACAP did not interfere with the gastrointestinal colonization of the pathogen, mice from the PACAP group exhibited less severe clinical signs of C. jejuni-induced disease, as compared to mock controls, which were paralleled by alleviated apoptotic, but enhanced cell proliferative responses in colonic epithelia on day 6 post-infection. Furthermore, PACAP dampened the accumulation of macrophages and monocytes, but enhanced regulatory T cell responses in the colon, which were accompanied by less IFN-γ secretion in intestinal compartments in PACAP versus mock-treated mice. Remarkably, the inflammation-dampening properties of PACAP could also be observed in extra-intestinal organs, and strikingly, even the systemic circulation on day 6 post-infection. For the first time, we provide evidence that synthetic PACAP might be a promising candidate to combat acute campylobacteriosis and post-infectious sequelae.

scholarly journals Immune-modulatory Properties of the Octapeptide NAP in Campylobacter jejuni Infected Mice Suffering from Acute Enterocolitis

2020 ◽  
Vol 8 (6) ◽  
pp. 802 ◽  
Author(s):  
Markus M. Heimesaat ◽  
Soraya Mousavi ◽  
Sigri Kløve ◽  
Claudia Genger ◽  
Dennis Weschka ◽  
...  
Keyword(s):  
Immune Responses ◽  
Campylobacter Jejuni ◽  
Post Infection ◽  
Intestinal Tract ◽  
Clinical Signs ◽  
Global Public Health ◽  
Food Borne ◽  
Human Infections ◽  
First Time ◽  
Post Infectious

Human infections with the food-borne zoonotic pathogen Campylobacter jejuni are progressively rising and constitute serious global public health and socioeconomic burdens. Hence, application of compounds with disease-alleviating properties are required to combat campylobacteriosis and post-infectious sequelae. In our preclinical intervention study applying an acute C. jejuni induced enterocolitis model, we surveyed the anti-pathogenic and immune-modulatory effects of the octapeptide NAP which is well-known for its neuroprotective and anti-inflammatory properties. Therefore, secondary abiotic IL-10−/− mice were perorally infected with C. jejuni and intraperitoneally treated with synthetic NAP from day 2 until day 5 post-infection. NAP-treatment did not affect gastrointestinal C. jejuni colonization but could alleviate clinical signs of infection that was accompanied by less pronounced apoptosis of colonic epithelial cells and enhancement of cell regenerative measures on day 6 post-infection. Moreover, NAP-treatment resulted in less distinct innate and adaptive pro-inflammatory immune responses that were not restricted to the intestinal tract but could also be observed in extra-intestinal and even systemic compartments. NAP-treatment further resulted in less frequent translocation of viable pathogens from the intestinal tract to extra-intestinal including systemic tissue sites. For the first time, we here provide evidence that NAP application constitutes a promising option to combat acute campylobacteriosis.

scholarly journals Identification of a Potential Receptor for Both Peptide Histidine Isoleucine and Peptide Histidine Valine

Endocrinology ◽  
2002 ◽  
Vol 143 (4) ◽  
pp. 1327-1336 ◽  
Author(s):  
Dicky Lai-Yin Tse ◽  
Ronald Ting-Kai Pang ◽  
Anderson On-Lam Wong ◽  
Siu-Ming Chan ◽  
Hubert Vaudry ◽  
...  
Keyword(s):  
Gall Bladder ◽  
Adenylate Cyclase ◽  
Chinese Hamster Ovary Cells ◽  
Receptor Gene ◽  
Chinese Hamster ◽  
Functional Expression ◽  
Coding Region ◽  
Ovary Cells ◽  
Pituitary Adenylate Cyclase ◽  
First Time

Abstract Peptide histidine isoleucine (PHI), peptide histidine valine (PHV), and vasoactive intestinal polypeptide (VIP) are cosynthesized from the same precursor and share high levels of structural similarities with overlapping biological functions. In this study, the first PHI/PHV receptor was isolated and characterized in goldfish. To study this receptor using homologous peptides, we have also characterized the goldfish prepro-PHI/VIP, and, surprisingly, a shorter transcript lacking the VIP coding region was isolated. A PHI/VIP precursor without the VIP coding sequence has never before been reported. Initial functional expression of the PHI/PHV receptor in Chinese hamster ovary cells revealed that it could be activated by human PHV [50% effective concentration (EC50): 43 nm] and to a lesser extent human PHI (EC50: 133 nm) and helodermin (EC50: 166 nm) but not fish and mammalian pituitary adenylate cyclase-activating polypeptides and VIPs. Subsequent studies indicated that, similar to the pituitary adenylate cyclase-activating polypeptide receptors (PAC1-R, VPAC1-R, and VPAC2-R), the receptor isolated in this study is able to interact with goldfish PHI and its C-terminally extended form, PHV with EC50 values 93 and 43 nm, respectively. Northern blot and RT-PCR/Southern blot analyses revealed that the PHI/VIP gene is expressed in the intestine, brain, and gall bladder and the PHI/PHV receptor gene is primarily expressed in the pituitary and to a lesser extend in the intestine and gall bladder, suggesting that PHI/PHV may play a role, notably in the regulation of pituitary function. In conclusion, our results demonstrate for the first time the existence of a PHI/PHV receptor, indicating that the functions of PHI and PHV could be mediated by their own receptor in addition to VIP receptors.

scholarly journals Treatment with the Probiotic Product Aviguard® Alleviates Inflammatory Responses during Campylobacter jejuni-Induced Acute Enterocolitis in Mice

2021 ◽  
Vol 22 (13) ◽  
pp. 6683
Author(s):  
Markus M. Heimesaat ◽  
Dennis Weschka ◽  
Soraya Mousavi ◽  
Stefan Bereswill
Keyword(s):  
Post Infection ◽  
Intestinal Tract ◽  
Inflammatory Responses ◽  
Apoptotic Cell ◽  
Feed Additives ◽  
Gastrointestinal Pathogen ◽  
Obligate Anaerobic ◽  
Probiotic Treatment ◽  
Probiotic Product ◽  
First Time

Prevalences of Campylobacter (C.) jejuni infections are progressively rising globally. Given that probiotic feed additives, such as the commercial product Aviguard®, have been shown to be effective in reducing enteropathogens, such as Salmonella, in vertebrates, including livestock, we assessed potential anti-pathogenic and immune-modulatory properties of Aviguard® during acute C. jejuni-induced murine enterocolitis. Therefore, microbiota-depleted IL-10−/− mice were infected with C. jejuni strain 81-176 by gavage and orally treated with Aviguard® or placebo from day 2 to 4 post-infection. The applied probiotic bacteria could be rescued from the intestinal tract of treated mice, but with lower obligate anaerobic bacterial counts in C. jejuni-infected as compared to non-infected mice. Whereas comparable gastrointestinal pathogen loads could be detected in both groups until day 6 post-infection, Aviguard® treatment resulted in improved clinical outcome and attenuated apoptotic cell responses in infected large intestines during acute campylobacteriosis. Furthermore, less distinct pro-inflammatory immune responses could be observed not only in the intestinal tract, but also in extra-intestinal compartments on day 6 post-infection. In conclusion, we show here for the first time that Aviguard® exerts potent disease-alleviating effects in acute C. jejuni-induced murine enterocolitis and might be a promising probiotic treatment option for severe campylobacteriosis in humans.

scholarly journals Diabetes Affects the Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP)-Like Immunoreactive Enteric Neurons in the Porcine Digestive Tract

2021 ◽  
Vol 22 (11) ◽  
pp. 5727
Author(s):  
Katarzyna Palus ◽  
Michał Bulc ◽  
Jarosław Całka ◽  
Łukasz Zielonka ◽  
Marcin Nowicki
Keyword(s):  
Adenylate Cyclase ◽  
Neuronal Development ◽  
Enteric Neurons ◽  
Double Labelling ◽  
Regulatory Processes ◽  
Inflammatory Conditions ◽  
Pituitary Adenylate Cyclase ◽  
Descending Colon ◽  
The Impact ◽  
First Time

Diabetic gastroenteropathy is a common complication, which develops in patients with long-term diabetes. The pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide known for its cytoprotective properties and plays an important role in neuronal development, neuromodulation and neuroprotection. The present study was designed to elucidate, for the first time, the impact of prolonged hyperglycaemia conditions on a population of PACAP-like immunoreactive neurons in selected parts of the porcine gastrointestinal tract. The experiment was conducted on 10 juvenile female pigs assigned to two experimental groups: The DM group (pigs with streptozocin-induced diabetes) and the C group (control pigs). Diabetes conditions were induced by a single intravenous injection of streptozocin. Six weeks after the induction of diabetes, all animals were euthanised and further collected, and fixed fragments of the stomach, duodenum, jejunum, ileum and descending colon were processed using the routine double-labelling immunofluorescence technique. Streptozotocin-induced hyperglycaemia caused a significant increase in the population of PACAP-containing enteric neurons in the porcine stomach, small intestines and descending colon. The recorded changes may result from the direct toxic effect of hyperglycaemia on the ENS neurons, oxidative stress or inflammatory conditions accompanying hyperglycaemia and suggest that PACAP is involved in regulatory processes of the GIT function in the course of diabetes.

scholarly journals Pituitary Adenylate Cyclase-Activating Polypeptide Receptors Mediating Insulin Secretion in Rodent Pancreatic Islets Are Coupled to Adenylate Cyclase But Not to PLC

Endocrinology ◽  
2002 ◽  
Vol 143 (4) ◽  
pp. 1253-1259 ◽  
Author(s):  
Francoise Jamen ◽  
Raymond Puech ◽  
Joel Bockaert ◽  
Philippe Brabet ◽  
Gyslaine Bertrand
Keyword(s):  
Insulin Secretion ◽  
Adenylate Cyclase ◽  
Pancreatic Islets ◽  
Pituitary Adenylate Cyclase

scholarly journals Purification and characterization of the receptor for pituitary adenylate cyclase-activating polypeptide.

1993 ◽  
Vol 268 (35) ◽  
pp. 26650-26657
Author(s):  
T Ohtaki ◽  
Y Masuda ◽  
Y Ishibashi ◽  
C Kitada ◽  
A Arimura ◽  
...  
Keyword(s):  
Adenylate Cyclase ◽  
Purification And Characterization ◽  
Pituitary Adenylate Cyclase
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