Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation.
Histamine 4 receptor (H4R) is a novel target for the pharmacological modulation of histamine-mediated immune signals during inflammatory diseases. The purpose of this study was to assess the effects of the H4R agonist 4-methylhistamine dihydrochloride (4-MeH) and antagonist JNJ7777120 (JNJ) in the i...
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| Format: | Article |
| Language: | English English |
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Elsevier
2015
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| Online Access: | http://irep.iium.edu.my/66890/ http://irep.iium.edu.my/66890/ http://irep.iium.edu.my/66890/ http://irep.iium.edu.my/66890/1/Regulation%20of%20TNF-%CE%B1%20and%20NF-%CE%BAB%20activation%20through%20the%20JAK%20STAT%20signaling%20pathway%20downstream%20of%20histamine%204%20receptor%20in%20a%20rat%20model%20of%20LPS-induced%20joint%20inflammation..pdf http://irep.iium.edu.my/66890/7/66890_Scopus.pdf |
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iium-668902019-01-04T08:39:20Z http://irep.iium.edu.my/66890/ Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. Ahmad, Sheikh Fayaz Ahmad Ansari, Mushtaq Zoheir, Khairy M.A. A.Bakheet, Saleh M.Korashy, Hesham Nadeem, Ahmed Ashour, Abdelkader Elbadawy Abbas Attia, Sabry M. RM300 Drugs and their action Histamine 4 receptor (H4R) is a novel target for the pharmacological modulation of histamine-mediated immune signals during inflammatory diseases. The purpose of this study was to assess the effects of the H4R agonist 4-methylhistamine dihydrochloride (4-MeH) and antagonist JNJ7777120 (JNJ) in the inflamed rat knee. Animals were fasted for 18h before a single dose of 4-MeH or JNJ (30mg/kg) was administered intraperitoneally (i.p.), both followed by intra-articular (i.a.) injection of LPS 2h later. Blood and synovial fluid were collected after a short incubation period and TNF-α, NF-κB, and IkB-α levels were measured via flow cytometry. Additionally, we assessed the effects of H4R engagement on the expression of IL-1β, TNF-α, and NF-κB mRNAs and the protein levels of TNF-α, NF-κB, JAK-1, and STAT-3 in the inflamed knee tissue. These results revealed increased TNF-α and NF-κB expression and decreased IkB-α levels in both the LPS alone and 4-MeH treated groups in whole blood and synovial fluid. Further, IL-1β, TNF-α, and NF-κB mRNA levels were significantly increased and western blot analysis confirmed increased expression of TNF-α, NF-κB, JAK-1, and STAT-3 in both LPS and 4-MeH treatment groups. Furthermore, these increases were completely inhibited in the inflamed knee tissue of the JNJ-treated group. Thus, the inhibition of inflammatory mediators and signaling pathways by the H4R antagonist JNJ suggests the anti-arthritic importance of this molecule. Elsevier 2015-07-01 Article PeerReviewed application/pdf en http://irep.iium.edu.my/66890/1/Regulation%20of%20TNF-%CE%B1%20and%20NF-%CE%BAB%20activation%20through%20the%20JAK%20STAT%20signaling%20pathway%20downstream%20of%20histamine%204%20receptor%20in%20a%20rat%20model%20of%20LPS-induced%20joint%20inflammation..pdf application/pdf en http://irep.iium.edu.my/66890/7/66890_Scopus.pdf Ahmad, Sheikh Fayaz and Ahmad Ansari, Mushtaq and Zoheir, Khairy M.A. and A.Bakheet, Saleh and M.Korashy, Hesham and Nadeem, Ahmed and Ashour, Abdelkader Elbadawy Abbas and Attia, Sabry M. (2015) Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. Immunobiology, 220 (7). pp. 889-898. ISSN 0171-2985 https://www.journals.elsevier.com/immunobiology/ doi.org/10.1016/j.imbio.2015.01.008 |
| repository_type |
Digital Repository |
| institution_category |
Local University |
| institution |
International Islamic University Malaysia |
| building |
IIUM Repository |
| collection |
Online Access |
| language |
English English |
| topic |
RM300 Drugs and their action |
| spellingShingle |
RM300 Drugs and their action Ahmad, Sheikh Fayaz Ahmad Ansari, Mushtaq Zoheir, Khairy M.A. A.Bakheet, Saleh M.Korashy, Hesham Nadeem, Ahmed Ashour, Abdelkader Elbadawy Abbas Attia, Sabry M. Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. |
| description |
Histamine 4 receptor (H4R) is a novel target for the pharmacological modulation of histamine-mediated immune signals during inflammatory diseases. The purpose of this study was to assess the effects of the H4R agonist 4-methylhistamine dihydrochloride (4-MeH) and antagonist JNJ7777120 (JNJ) in the inflamed rat knee. Animals were fasted for 18h before a single dose of 4-MeH or JNJ (30mg/kg) was administered intraperitoneally (i.p.), both followed by intra-articular (i.a.) injection of LPS 2h later. Blood and synovial fluid were collected after a short incubation period and TNF-α, NF-κB, and IkB-α levels were measured via flow cytometry. Additionally, we assessed the effects of H4R engagement on the expression of IL-1β, TNF-α, and NF-κB mRNAs and the protein levels of TNF-α, NF-κB, JAK-1, and STAT-3 in the inflamed knee tissue. These results revealed increased TNF-α and NF-κB expression and decreased IkB-α levels in both the LPS alone and 4-MeH treated groups in whole blood and synovial fluid. Further, IL-1β, TNF-α, and NF-κB mRNA levels were significantly increased and western blot analysis confirmed increased expression of TNF-α, NF-κB, JAK-1, and STAT-3 in both LPS and 4-MeH treatment groups. Furthermore, these increases were completely inhibited in the inflamed knee tissue of the JNJ-treated group. Thus, the inhibition of inflammatory mediators and signaling pathways by the H4R antagonist JNJ suggests the anti-arthritic importance of this molecule. |
| format |
Article |
| author |
Ahmad, Sheikh Fayaz Ahmad Ansari, Mushtaq Zoheir, Khairy M.A. A.Bakheet, Saleh M.Korashy, Hesham Nadeem, Ahmed Ashour, Abdelkader Elbadawy Abbas Attia, Sabry M. |
| author_facet |
Ahmad, Sheikh Fayaz Ahmad Ansari, Mushtaq Zoheir, Khairy M.A. A.Bakheet, Saleh M.Korashy, Hesham Nadeem, Ahmed Ashour, Abdelkader Elbadawy Abbas Attia, Sabry M. |
| author_sort |
Ahmad, Sheikh Fayaz |
| title |
Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. |
| title_short |
Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. |
| title_full |
Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. |
| title_fullStr |
Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. |
| title_full_unstemmed |
Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. |
| title_sort |
regulation of tnf-α and nf-κb activation through the jak/stat signaling pathway downstream of histamine 4 receptor in a rat model of lps-induced joint inflammation. |
| publisher |
Elsevier |
| publishDate |
2015 |
| url |
http://irep.iium.edu.my/66890/ http://irep.iium.edu.my/66890/ http://irep.iium.edu.my/66890/ http://irep.iium.edu.my/66890/1/Regulation%20of%20TNF-%CE%B1%20and%20NF-%CE%BAB%20activation%20through%20the%20JAK%20STAT%20signaling%20pathway%20downstream%20of%20histamine%204%20receptor%20in%20a%20rat%20model%20of%20LPS-induced%20joint%20inflammation..pdf http://irep.iium.edu.my/66890/7/66890_Scopus.pdf |
| first_indexed |
2023-09-18T21:34:58Z |
| last_indexed |
2023-09-18T21:34:58Z |
| _version_ |
1777412759512678400 |