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Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin
Introduction The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mou...
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Published in: | Advances in therapy 2008-12, Vol.25 (12), p.1331-1341 |
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creator | Wang, Jiang Zhao, Rong Zhang, Fuqin Li, Jianping Huo, Binliang Cao, Yunxin Dou, Kefeng |
description | Introduction
The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mouse model of skin transplantation and the effects of CST on T lymphocytes.
Methods
BALB/c (H-2K
d
) recipient mice (
n
=70) were divided into seven groups (
n
=10 per group) and given an intraperitoneal injection of CST or a somatostatin analog, SMS 201-995 (octreotide), on the day of skin transplantation from C57BL/6 (B6) (H-2K
b
) donors. Injections were continued for 7 consecutive days. Groups 1-3 received CST at doses of 0.02, 0.2, or 2 mg/kg, respectively. Groups 4–6 received SMS 201–995 at the same doses. Group 7 was a control group and received injections of phosphate buffered saline. Survival of the allografts was recorded. A semiquantitative reverse transcriptase polymerase chain reaction study of Foxp3 expression and a flow cytometry study of CD4 and CD25 markers of T lymphocytes were conducted to determine whether CD4
+
CD25
+
Foxp3
high
regulatory T cells (T
reg
) were generated in vivo.
Results
BALB/c mice given CST (0.2 or 2 mg/kg) had prolonged graft survival (median survival time [MST], 13 and 14 days, respectively;
P |
doi_str_mv | 10.1007/s12325-008-0121-z |
format | article |
fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_733916553</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>733916553</sourcerecordid><originalsourceid>FETCH-LOGICAL-c374t-953a5e234252e58f96fd717ec7cd512400d07f1337512fbdc4c02f9254d9d6b83</originalsourceid><addsrcrecordid>eNp9kMFKJDEQhoMoOqs-wF6WnNzLtlaSTqf7uAzuriB4UfAWMunKkKEnaZO0MD69PczA3jwURVHf_x8-Qr4zuGUA6i4zLrisANoKGGfVxwlZsLaR1Tz8lCxA1azion29IN9y3gBwULI9JxesA1GLTi3I8zKGkuJAo6NmGOI6GVdowg3a4mOgPtCtt0hXO2rGcdj5sKaGhviOAw04pTjiWHyPv6iNqfhcTPHhipw5M2S8Pu5L8vLn_nn5r3p8-vuw_P1YWaHqUnVSGIlc1FxylK3rGtcrptAq20vGa4AelGNCqPlyq97WFrjruKz7rm9WrbgkPw-9Y4pvE-aitz5bHAYTME5ZKyE61kgpZvLmS5Iz1oCU-0p2AG2KOSd0ekx-a9JOM9B76fogXc_S9V66_pgzP47l02qL_f_E0fIM8AOQ51dYY9KbOKUwq_mi9RNc2I0X</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>21160558</pqid></control><display><type>article</type><title>Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin</title><source>Springer Nature</source><creator>Wang, Jiang ; Zhao, Rong ; Zhang, Fuqin ; Li, Jianping ; Huo, Binliang ; Cao, Yunxin ; Dou, Kefeng</creator><creatorcontrib>Wang, Jiang ; Zhao, Rong ; Zhang, Fuqin ; Li, Jianping ; Huo, Binliang ; Cao, Yunxin ; Dou, Kefeng</creatorcontrib><description>Introduction
The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mouse model of skin transplantation and the effects of CST on T lymphocytes.
Methods
BALB/c (H-2K
d
) recipient mice (
n
=70) were divided into seven groups (
n
=10 per group) and given an intraperitoneal injection of CST or a somatostatin analog, SMS 201-995 (octreotide), on the day of skin transplantation from C57BL/6 (B6) (H-2K
b
) donors. Injections were continued for 7 consecutive days. Groups 1-3 received CST at doses of 0.02, 0.2, or 2 mg/kg, respectively. Groups 4–6 received SMS 201–995 at the same doses. Group 7 was a control group and received injections of phosphate buffered saline. Survival of the allografts was recorded. A semiquantitative reverse transcriptase polymerase chain reaction study of Foxp3 expression and a flow cytometry study of CD4 and CD25 markers of T lymphocytes were conducted to determine whether CD4
+
CD25
+
Foxp3
high
regulatory T cells (T
reg
) were generated in vivo.
Results
BALB/c mice given CST (0.2 or 2 mg/kg) had prolonged graft survival (median survival time [MST], 13 and 14 days, respectively;
P
<0.05 compared with controls). SMS 201–995 at the same concentrations did not have a significant effect on allograft survival (MST, 8 days for both groups). We found more than a twofold increase of CD4
+
CD25
+
T
reg
cells in the CD4
+
T-cell population and the expression of Foxp3 was up-regulated in the CST treatment groups, compared with control and SMS 201-995 treatment groups.
Conclusion
In our study, CST induced a significant prolongation in survival time of allogeneic skin grafts and increased the generation of CD4
+
CD25
+
Foxp 3
high
T
reg
cells. These results suggest that CST may become a new modality in controlling allograft rejection.</description><identifier>ISSN: 0741-238X</identifier><identifier>EISSN: 1865-8652</identifier><identifier>DOI: 10.1007/s12325-008-0121-z</identifier><identifier>PMID: 19034397</identifier><language>eng</language><publisher>Heidelberg: Springer Healthcare Communications</publisher><subject>Animals ; Cardiology ; Endocrinology ; Flow Cytometry ; Forkhead Transcription Factors - biosynthesis ; Graft Rejection - immunology ; Graft Rejection - metabolism ; Graft Rejection - prevention & control ; Health technology assessment ; Immunologic Factors - therapeutic use ; Interleukin-2 Receptor alpha Subunit - metabolism ; Internal Medicine ; Male ; Medicine ; Medicine & Public Health ; Mice ; Mice, Inbred BALB C ; Neuropeptides - therapeutic use ; Octreotide - therapeutic use ; Oncology ; Original Research ; Pharmacology/Toxicology ; Reverse Transcriptase Polymerase Chain Reaction ; Rheumatology ; Skin Transplantation - immunology ; T-Lymphocytes, Regulatory - immunology ; T-Lymphocytes, Regulatory - metabolism</subject><ispartof>Advances in therapy, 2008-12, Vol.25 (12), p.1331-1341</ispartof><rights>Springer Healthcare Communications 2008</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c374t-953a5e234252e58f96fd717ec7cd512400d07f1337512fbdc4c02f9254d9d6b83</citedby><cites>FETCH-LOGICAL-c374t-953a5e234252e58f96fd717ec7cd512400d07f1337512fbdc4c02f9254d9d6b83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27915,27916</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19034397$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Jiang</creatorcontrib><creatorcontrib>Zhao, Rong</creatorcontrib><creatorcontrib>Zhang, Fuqin</creatorcontrib><creatorcontrib>Li, Jianping</creatorcontrib><creatorcontrib>Huo, Binliang</creatorcontrib><creatorcontrib>Cao, Yunxin</creatorcontrib><creatorcontrib>Dou, Kefeng</creatorcontrib><title>Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin</title><title>Advances in therapy</title><addtitle>Adv Therapy</addtitle><addtitle>Adv Ther</addtitle><description>Introduction
The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mouse model of skin transplantation and the effects of CST on T lymphocytes.
Methods
BALB/c (H-2K
d
) recipient mice (
n
=70) were divided into seven groups (
n
=10 per group) and given an intraperitoneal injection of CST or a somatostatin analog, SMS 201-995 (octreotide), on the day of skin transplantation from C57BL/6 (B6) (H-2K
b
) donors. Injections were continued for 7 consecutive days. Groups 1-3 received CST at doses of 0.02, 0.2, or 2 mg/kg, respectively. Groups 4–6 received SMS 201–995 at the same doses. Group 7 was a control group and received injections of phosphate buffered saline. Survival of the allografts was recorded. A semiquantitative reverse transcriptase polymerase chain reaction study of Foxp3 expression and a flow cytometry study of CD4 and CD25 markers of T lymphocytes were conducted to determine whether CD4
+
CD25
+
Foxp3
high
regulatory T cells (T
reg
) were generated in vivo.
Results
BALB/c mice given CST (0.2 or 2 mg/kg) had prolonged graft survival (median survival time [MST], 13 and 14 days, respectively;
P
<0.05 compared with controls). SMS 201–995 at the same concentrations did not have a significant effect on allograft survival (MST, 8 days for both groups). We found more than a twofold increase of CD4
+
CD25
+
T
reg
cells in the CD4
+
T-cell population and the expression of Foxp3 was up-regulated in the CST treatment groups, compared with control and SMS 201-995 treatment groups.
Conclusion
In our study, CST induced a significant prolongation in survival time of allogeneic skin grafts and increased the generation of CD4
+
CD25
+
Foxp 3
high
T
reg
cells. These results suggest that CST may become a new modality in controlling allograft rejection.</description><subject>Animals</subject><subject>Cardiology</subject><subject>Endocrinology</subject><subject>Flow Cytometry</subject><subject>Forkhead Transcription Factors - biosynthesis</subject><subject>Graft Rejection - immunology</subject><subject>Graft Rejection - metabolism</subject><subject>Graft Rejection - prevention & control</subject><subject>Health technology assessment</subject><subject>Immunologic Factors - therapeutic use</subject><subject>Interleukin-2 Receptor alpha Subunit - metabolism</subject><subject>Internal Medicine</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine & Public Health</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Neuropeptides - therapeutic use</subject><subject>Octreotide - therapeutic use</subject><subject>Oncology</subject><subject>Original Research</subject><subject>Pharmacology/Toxicology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Rheumatology</subject><subject>Skin Transplantation - immunology</subject><subject>T-Lymphocytes, Regulatory - immunology</subject><subject>T-Lymphocytes, Regulatory - metabolism</subject><issn>0741-238X</issn><issn>1865-8652</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNp9kMFKJDEQhoMoOqs-wF6WnNzLtlaSTqf7uAzuriB4UfAWMunKkKEnaZO0MD69PczA3jwURVHf_x8-Qr4zuGUA6i4zLrisANoKGGfVxwlZsLaR1Tz8lCxA1azion29IN9y3gBwULI9JxesA1GLTi3I8zKGkuJAo6NmGOI6GVdowg3a4mOgPtCtt0hXO2rGcdj5sKaGhviOAw04pTjiWHyPv6iNqfhcTPHhipw5M2S8Pu5L8vLn_nn5r3p8-vuw_P1YWaHqUnVSGIlc1FxylK3rGtcrptAq20vGa4AelGNCqPlyq97WFrjruKz7rm9WrbgkPw-9Y4pvE-aitz5bHAYTME5ZKyE61kgpZvLmS5Iz1oCU-0p2AG2KOSd0ekx-a9JOM9B76fogXc_S9V66_pgzP47l02qL_f_E0fIM8AOQ51dYY9KbOKUwq_mi9RNc2I0X</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>Wang, Jiang</creator><creator>Zhao, Rong</creator><creator>Zhang, Fuqin</creator><creator>Li, Jianping</creator><creator>Huo, Binliang</creator><creator>Cao, Yunxin</creator><creator>Dou, Kefeng</creator><general>Springer Healthcare Communications</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>20081201</creationdate><title>Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin</title><author>Wang, Jiang ; Zhao, Rong ; Zhang, Fuqin ; Li, Jianping ; Huo, Binliang ; Cao, Yunxin ; Dou, Kefeng</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c374t-953a5e234252e58f96fd717ec7cd512400d07f1337512fbdc4c02f9254d9d6b83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Cardiology</topic><topic>Endocrinology</topic><topic>Flow Cytometry</topic><topic>Forkhead Transcription Factors - biosynthesis</topic><topic>Graft Rejection - immunology</topic><topic>Graft Rejection - metabolism</topic><topic>Graft Rejection - prevention & control</topic><topic>Health technology assessment</topic><topic>Immunologic Factors - therapeutic use</topic><topic>Interleukin-2 Receptor alpha Subunit - metabolism</topic><topic>Internal Medicine</topic><topic>Male</topic><topic>Medicine</topic><topic>Medicine & Public Health</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Neuropeptides - therapeutic use</topic><topic>Octreotide - therapeutic use</topic><topic>Oncology</topic><topic>Original Research</topic><topic>Pharmacology/Toxicology</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>Rheumatology</topic><topic>Skin Transplantation - immunology</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>T-Lymphocytes, Regulatory - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Jiang</creatorcontrib><creatorcontrib>Zhao, Rong</creatorcontrib><creatorcontrib>Zhang, Fuqin</creatorcontrib><creatorcontrib>Li, Jianping</creatorcontrib><creatorcontrib>Huo, Binliang</creatorcontrib><creatorcontrib>Cao, Yunxin</creatorcontrib><creatorcontrib>Dou, Kefeng</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Immunology Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Advances in therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Jiang</au><au>Zhao, Rong</au><au>Zhang, Fuqin</au><au>Li, Jianping</au><au>Huo, Binliang</au><au>Cao, Yunxin</au><au>Dou, Kefeng</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin</atitle><jtitle>Advances in therapy</jtitle><stitle>Adv Therapy</stitle><addtitle>Adv Ther</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>25</volume><issue>12</issue><spage>1331</spage><epage>1341</epage><pages>1331-1341</pages><issn>0741-238X</issn><eissn>1865-8652</eissn><abstract>Introduction
The action of cortistatin (CST), a novel cyclic neuropeptide, as an anti-inflammatory factor has been studied, but few investigations have explored the immunomodulatory role of CST in transplantation. In the present study, we examined whether CST affects the alloimmune response in a mouse model of skin transplantation and the effects of CST on T lymphocytes.
Methods
BALB/c (H-2K
d
) recipient mice (
n
=70) were divided into seven groups (
n
=10 per group) and given an intraperitoneal injection of CST or a somatostatin analog, SMS 201-995 (octreotide), on the day of skin transplantation from C57BL/6 (B6) (H-2K
b
) donors. Injections were continued for 7 consecutive days. Groups 1-3 received CST at doses of 0.02, 0.2, or 2 mg/kg, respectively. Groups 4–6 received SMS 201–995 at the same doses. Group 7 was a control group and received injections of phosphate buffered saline. Survival of the allografts was recorded. A semiquantitative reverse transcriptase polymerase chain reaction study of Foxp3 expression and a flow cytometry study of CD4 and CD25 markers of T lymphocytes were conducted to determine whether CD4
+
CD25
+
Foxp3
high
regulatory T cells (T
reg
) were generated in vivo.
Results
BALB/c mice given CST (0.2 or 2 mg/kg) had prolonged graft survival (median survival time [MST], 13 and 14 days, respectively;
P
<0.05 compared with controls). SMS 201–995 at the same concentrations did not have a significant effect on allograft survival (MST, 8 days for both groups). We found more than a twofold increase of CD4
+
CD25
+
T
reg
cells in the CD4
+
T-cell population and the expression of Foxp3 was up-regulated in the CST treatment groups, compared with control and SMS 201-995 treatment groups.
Conclusion
In our study, CST induced a significant prolongation in survival time of allogeneic skin grafts and increased the generation of CD4
+
CD25
+
Foxp 3
high
T
reg
cells. These results suggest that CST may become a new modality in controlling allograft rejection.</abstract><cop>Heidelberg</cop><pub>Springer Healthcare Communications</pub><pmid>19034397</pmid><doi>10.1007/s12325-008-0121-z</doi><tpages>11</tpages></addata></record> |
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source | Springer Nature |
subjects | Animals Cardiology Endocrinology Flow Cytometry Forkhead Transcription Factors - biosynthesis Graft Rejection - immunology Graft Rejection - metabolism Graft Rejection - prevention & control Health technology assessment Immunologic Factors - therapeutic use Interleukin-2 Receptor alpha Subunit - metabolism Internal Medicine Male Medicine Medicine & Public Health Mice Mice, Inbred BALB C Neuropeptides - therapeutic use Octreotide - therapeutic use Oncology Original Research Pharmacology/Toxicology Reverse Transcriptase Polymerase Chain Reaction Rheumatology Skin Transplantation - immunology T-Lymphocytes, Regulatory - immunology T-Lymphocytes, Regulatory - metabolism |
title | Control of allograft rejection in mice by applying a novel neuropeptide, cortistatin |
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