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Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models
OBJECTIVE: CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally bioavailable molecule known to suppress in vitro the production of tumor necrosis factor-alpha (TNF-alpha). We evaluated its therapeutic potential and antiinflammatory effects in 3 murine models of adjuvant induced arthriti...
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| Published in: | Journal of rheumatology 2005-03, Vol.32 (3), p.469-476 |
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| Main Authors: | , , , , , , , , |
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| container_end_page | 476 |
| container_issue | 3 |
| container_start_page | 469 |
| container_title | Journal of rheumatology |
| container_volume | 32 |
| creator | BAHARAV, Ehud BAR-YEHUDA, Sara MADI, Lea SILBERMAN, Daniel RATH-WOLFSON, Lea HALPREN, Marisa OCHAION, Avivit WEINBERGER, Abraham FISHMAN, Pnina |
| description | OBJECTIVE: CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally bioavailable molecule known to suppress in vitro
the production of tumor necrosis factor-alpha (TNF-alpha). We evaluated its therapeutic potential and antiinflammatory effects
in 3 murine models of adjuvant induced arthritis (AIA). METHODS: The antiinflammatory effect of CF101 was examined in rat
AIA, in mouse collagen induced arthritis, and in tropomyosin induced arthritis. The clinical effect of another A3AR agonist,
Cl-IB-MECA, was examined in rat AIA. The effect of low dose (10 or 100 mg/kg/day) A3AR agonists administered orally once daily
on arthritis severity was assessed clinically and histologically. The effect of CF101 on the protein expression level of TNF-alpha
in the synovial tissue, draining lymph nodes, and spleen cells was determined by Western blot. RESULTS: CF101 and Cl-IB-MECA
markedly ameliorated the clinical and histological features of arthritis in the 3 models when administered orally at a low
dose of 10 mg/kg body weight in the 3 autoimmune arthritis models. The lower dose of 10 mg/kg of either CF101 or Cl-IB-MECA
had better antiinflammatory effect than the higher 100 mg/kg dose. Decreased expression of TNF-alpha was noted in protein
extracts of synovia, draining lymph nodes, and spleen tissues. CONCLUSION: The results provide evidence that A3AR agonists
exert significant antirheumatic effects in different autoimmune arthritis models by suppression of TNF-alpha production. The
beneficial activity of the drugs at the low dose demonstrates that the effect is A3AR mediated. |
| format | article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_67479488</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>67479488</sourcerecordid><originalsourceid>FETCH-LOGICAL-h269t-a044fc9464109ae9c551f5c4b7dd8fafe44c4183fca75d41e459d38fbe2777d63</originalsourceid><addsrcrecordid>eNpF0F9LwzAUBfAiipvTryB50bdC09wmzeMY_oOBLwq-hSy9WSNNO5OUsm_vhpM93QPnx3m4F9mcgpR5KaryMpsXjFY55eXXLLuJ8bsoKAdeX2czWgkogdXzTC375FxvO-29TkPYE7QWTSKDJUtGdIP9EF2PJKDB3QEQvR16F1Mkrid-DMdOj2lw3o_HGFIbXHKR-KHBLt5mV1Z3Ee9Od5F9Pj99rF7z9fvL22q5ztuSy5TrAsAaCRxoITVKU1XUVgY2omlqqy0CGKA1s0aLqgGKUMmG1XaDpRCi4WyRPf7t7sLwM2JMyrtosOt0j8MYFRcgJNT1Ad6f4Ljx2KhdcF6Hvfp_yQE8nICORnc26N64eHacF2UN7Oxat20nF1BFr7vuMMvUNE2sVEwBl-wXc7h6FQ</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>67479488</pqid></control><display><type>article</type><title>Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models</title><source>Freely Accessible Journals</source><creator>BAHARAV, Ehud ; BAR-YEHUDA, Sara ; MADI, Lea ; SILBERMAN, Daniel ; RATH-WOLFSON, Lea ; HALPREN, Marisa ; OCHAION, Avivit ; WEINBERGER, Abraham ; FISHMAN, Pnina</creator><creatorcontrib>BAHARAV, Ehud ; BAR-YEHUDA, Sara ; MADI, Lea ; SILBERMAN, Daniel ; RATH-WOLFSON, Lea ; HALPREN, Marisa ; OCHAION, Avivit ; WEINBERGER, Abraham ; FISHMAN, Pnina</creatorcontrib><description>OBJECTIVE: CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally bioavailable molecule known to suppress in vitro
the production of tumor necrosis factor-alpha (TNF-alpha). We evaluated its therapeutic potential and antiinflammatory effects
in 3 murine models of adjuvant induced arthritis (AIA). METHODS: The antiinflammatory effect of CF101 was examined in rat
AIA, in mouse collagen induced arthritis, and in tropomyosin induced arthritis. The clinical effect of another A3AR agonist,
Cl-IB-MECA, was examined in rat AIA. The effect of low dose (10 or 100 mg/kg/day) A3AR agonists administered orally once daily
on arthritis severity was assessed clinically and histologically. The effect of CF101 on the protein expression level of TNF-alpha
in the synovial tissue, draining lymph nodes, and spleen cells was determined by Western blot. RESULTS: CF101 and Cl-IB-MECA
markedly ameliorated the clinical and histological features of arthritis in the 3 models when administered orally at a low
dose of 10 mg/kg body weight in the 3 autoimmune arthritis models. The lower dose of 10 mg/kg of either CF101 or Cl-IB-MECA
had better antiinflammatory effect than the higher 100 mg/kg dose. Decreased expression of TNF-alpha was noted in protein
extracts of synovia, draining lymph nodes, and spleen tissues. CONCLUSION: The results provide evidence that A3AR agonists
exert significant antirheumatic effects in different autoimmune arthritis models by suppression of TNF-alpha production. The
beneficial activity of the drugs at the low dose demonstrates that the effect is A3AR mediated.</description><identifier>ISSN: 0315-162X</identifier><identifier>EISSN: 1499-2752</identifier><identifier>PMID: 15742438</identifier><identifier>CODEN: JRHUA9</identifier><language>eng</language><publisher>Toronto, ON: The Journal of Rheumatology</publisher><subject>Adenosine - analogs & derivatives ; Adenosine - pharmacology ; Adenosine - therapeutic use ; Adenosine A3 Receptor Agonists ; Adenosine A3 Receptor Antagonists ; Animals ; Anti-Inflammatory Agents - pharmacology ; Anti-Inflammatory Agents - therapeutic use ; Arthritis, Experimental - drug therapy ; Arthritis, Experimental - pathology ; Bacterial arthritis and osteitis ; Bacterial diseases ; Biological and medical sciences ; Bones, joints and connective tissue. Antiinflammatory agents ; Collagen - immunology ; Diseases of the osteoarticular system ; Dose-Response Relationship, Drug ; Female ; Human bacterial diseases ; Infectious diseases ; Joints - drug effects ; Joints - immunology ; Joints - pathology ; Lymph Nodes - immunology ; Male ; Medical sciences ; Mice ; Mice, Inbred DBA ; Miscellaneous. Osteoarticular involvement in other diseases ; Pharmacology. Drug treatments ; Quinazolines - pharmacology ; Rats ; Receptor, Adenosine A3 - metabolism ; Spleen - immunology ; Triazoles - pharmacology ; Tumor Necrosis Factor-alpha - metabolism</subject><ispartof>Journal of rheumatology, 2005-03, Vol.32 (3), p.469-476</ispartof><rights>2005 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=16602843$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15742438$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>BAHARAV, Ehud</creatorcontrib><creatorcontrib>BAR-YEHUDA, Sara</creatorcontrib><creatorcontrib>MADI, Lea</creatorcontrib><creatorcontrib>SILBERMAN, Daniel</creatorcontrib><creatorcontrib>RATH-WOLFSON, Lea</creatorcontrib><creatorcontrib>HALPREN, Marisa</creatorcontrib><creatorcontrib>OCHAION, Avivit</creatorcontrib><creatorcontrib>WEINBERGER, Abraham</creatorcontrib><creatorcontrib>FISHMAN, Pnina</creatorcontrib><title>Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models</title><title>Journal of rheumatology</title><addtitle>J Rheumatol</addtitle><description>OBJECTIVE: CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally bioavailable molecule known to suppress in vitro
the production of tumor necrosis factor-alpha (TNF-alpha). We evaluated its therapeutic potential and antiinflammatory effects
in 3 murine models of adjuvant induced arthritis (AIA). METHODS: The antiinflammatory effect of CF101 was examined in rat
AIA, in mouse collagen induced arthritis, and in tropomyosin induced arthritis. The clinical effect of another A3AR agonist,
Cl-IB-MECA, was examined in rat AIA. The effect of low dose (10 or 100 mg/kg/day) A3AR agonists administered orally once daily
on arthritis severity was assessed clinically and histologically. The effect of CF101 on the protein expression level of TNF-alpha
in the synovial tissue, draining lymph nodes, and spleen cells was determined by Western blot. RESULTS: CF101 and Cl-IB-MECA
markedly ameliorated the clinical and histological features of arthritis in the 3 models when administered orally at a low
dose of 10 mg/kg body weight in the 3 autoimmune arthritis models. The lower dose of 10 mg/kg of either CF101 or Cl-IB-MECA
had better antiinflammatory effect than the higher 100 mg/kg dose. Decreased expression of TNF-alpha was noted in protein
extracts of synovia, draining lymph nodes, and spleen tissues. CONCLUSION: The results provide evidence that A3AR agonists
exert significant antirheumatic effects in different autoimmune arthritis models by suppression of TNF-alpha production. The
beneficial activity of the drugs at the low dose demonstrates that the effect is A3AR mediated.</description><subject>Adenosine - analogs & derivatives</subject><subject>Adenosine - pharmacology</subject><subject>Adenosine - therapeutic use</subject><subject>Adenosine A3 Receptor Agonists</subject><subject>Adenosine A3 Receptor Antagonists</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Anti-Inflammatory Agents - therapeutic use</subject><subject>Arthritis, Experimental - drug therapy</subject><subject>Arthritis, Experimental - pathology</subject><subject>Bacterial arthritis and osteitis</subject><subject>Bacterial diseases</subject><subject>Biological and medical sciences</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Collagen - immunology</subject><subject>Diseases of the osteoarticular system</subject><subject>Dose-Response Relationship, Drug</subject><subject>Female</subject><subject>Human bacterial diseases</subject><subject>Infectious diseases</subject><subject>Joints - drug effects</subject><subject>Joints - immunology</subject><subject>Joints - pathology</subject><subject>Lymph Nodes - immunology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred DBA</subject><subject>Miscellaneous. Osteoarticular involvement in other diseases</subject><subject>Pharmacology. Drug treatments</subject><subject>Quinazolines - pharmacology</subject><subject>Rats</subject><subject>Receptor, Adenosine A3 - metabolism</subject><subject>Spleen - immunology</subject><subject>Triazoles - pharmacology</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><issn>0315-162X</issn><issn>1499-2752</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNpF0F9LwzAUBfAiipvTryB50bdC09wmzeMY_oOBLwq-hSy9WSNNO5OUsm_vhpM93QPnx3m4F9mcgpR5KaryMpsXjFY55eXXLLuJ8bsoKAdeX2czWgkogdXzTC375FxvO-29TkPYE7QWTSKDJUtGdIP9EF2PJKDB3QEQvR16F1Mkrid-DMdOj2lw3o_HGFIbXHKR-KHBLt5mV1Z3Ee9Od5F9Pj99rF7z9fvL22q5ztuSy5TrAsAaCRxoITVKU1XUVgY2omlqqy0CGKA1s0aLqgGKUMmG1XaDpRCi4WyRPf7t7sLwM2JMyrtosOt0j8MYFRcgJNT1Ad6f4Ljx2KhdcF6Hvfp_yQE8nICORnc26N64eHacF2UN7Oxat20nF1BFr7vuMMvUNE2sVEwBl-wXc7h6FQ</recordid><startdate>20050301</startdate><enddate>20050301</enddate><creator>BAHARAV, Ehud</creator><creator>BAR-YEHUDA, Sara</creator><creator>MADI, Lea</creator><creator>SILBERMAN, Daniel</creator><creator>RATH-WOLFSON, Lea</creator><creator>HALPREN, Marisa</creator><creator>OCHAION, Avivit</creator><creator>WEINBERGER, Abraham</creator><creator>FISHMAN, Pnina</creator><general>The Journal of Rheumatology</general><general>Journal of Rheumatology Publishing</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20050301</creationdate><title>Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models</title><author>BAHARAV, Ehud ; BAR-YEHUDA, Sara ; MADI, Lea ; SILBERMAN, Daniel ; RATH-WOLFSON, Lea ; HALPREN, Marisa ; OCHAION, Avivit ; WEINBERGER, Abraham ; FISHMAN, Pnina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h269t-a044fc9464109ae9c551f5c4b7dd8fafe44c4183fca75d41e459d38fbe2777d63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Adenosine - analogs & derivatives</topic><topic>Adenosine - pharmacology</topic><topic>Adenosine - therapeutic use</topic><topic>Adenosine A3 Receptor Agonists</topic><topic>Adenosine A3 Receptor Antagonists</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Anti-Inflammatory Agents - therapeutic use</topic><topic>Arthritis, Experimental - drug therapy</topic><topic>Arthritis, Experimental - pathology</topic><topic>Bacterial arthritis and osteitis</topic><topic>Bacterial diseases</topic><topic>Biological and medical sciences</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Collagen - immunology</topic><topic>Diseases of the osteoarticular system</topic><topic>Dose-Response Relationship, Drug</topic><topic>Female</topic><topic>Human bacterial diseases</topic><topic>Infectious diseases</topic><topic>Joints - drug effects</topic><topic>Joints - immunology</topic><topic>Joints - pathology</topic><topic>Lymph Nodes - immunology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred DBA</topic><topic>Miscellaneous. Osteoarticular involvement in other diseases</topic><topic>Pharmacology. Drug treatments</topic><topic>Quinazolines - pharmacology</topic><topic>Rats</topic><topic>Receptor, Adenosine A3 - metabolism</topic><topic>Spleen - immunology</topic><topic>Triazoles - pharmacology</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>BAHARAV, Ehud</creatorcontrib><creatorcontrib>BAR-YEHUDA, Sara</creatorcontrib><creatorcontrib>MADI, Lea</creatorcontrib><creatorcontrib>SILBERMAN, Daniel</creatorcontrib><creatorcontrib>RATH-WOLFSON, Lea</creatorcontrib><creatorcontrib>HALPREN, Marisa</creatorcontrib><creatorcontrib>OCHAION, Avivit</creatorcontrib><creatorcontrib>WEINBERGER, Abraham</creatorcontrib><creatorcontrib>FISHMAN, Pnina</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of rheumatology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>BAHARAV, Ehud</au><au>BAR-YEHUDA, Sara</au><au>MADI, Lea</au><au>SILBERMAN, Daniel</au><au>RATH-WOLFSON, Lea</au><au>HALPREN, Marisa</au><au>OCHAION, Avivit</au><au>WEINBERGER, Abraham</au><au>FISHMAN, Pnina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models</atitle><jtitle>Journal of rheumatology</jtitle><addtitle>J Rheumatol</addtitle><date>2005-03-01</date><risdate>2005</risdate><volume>32</volume><issue>3</issue><spage>469</spage><epage>476</epage><pages>469-476</pages><issn>0315-162X</issn><eissn>1499-2752</eissn><coden>JRHUA9</coden><abstract>OBJECTIVE: CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally bioavailable molecule known to suppress in vitro
the production of tumor necrosis factor-alpha (TNF-alpha). We evaluated its therapeutic potential and antiinflammatory effects
in 3 murine models of adjuvant induced arthritis (AIA). METHODS: The antiinflammatory effect of CF101 was examined in rat
AIA, in mouse collagen induced arthritis, and in tropomyosin induced arthritis. The clinical effect of another A3AR agonist,
Cl-IB-MECA, was examined in rat AIA. The effect of low dose (10 or 100 mg/kg/day) A3AR agonists administered orally once daily
on arthritis severity was assessed clinically and histologically. The effect of CF101 on the protein expression level of TNF-alpha
in the synovial tissue, draining lymph nodes, and spleen cells was determined by Western blot. RESULTS: CF101 and Cl-IB-MECA
markedly ameliorated the clinical and histological features of arthritis in the 3 models when administered orally at a low
dose of 10 mg/kg body weight in the 3 autoimmune arthritis models. The lower dose of 10 mg/kg of either CF101 or Cl-IB-MECA
had better antiinflammatory effect than the higher 100 mg/kg dose. Decreased expression of TNF-alpha was noted in protein
extracts of synovia, draining lymph nodes, and spleen tissues. CONCLUSION: The results provide evidence that A3AR agonists
exert significant antirheumatic effects in different autoimmune arthritis models by suppression of TNF-alpha production. The
beneficial activity of the drugs at the low dose demonstrates that the effect is A3AR mediated.</abstract><cop>Toronto, ON</cop><pub>The Journal of Rheumatology</pub><pmid>15742438</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Journal of rheumatology, 2005-03, Vol.32 (3), p.469-476 |
| issn | 0315-162X 1499-2752 |
| language | eng |
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| source | Freely Accessible Journals |
| subjects | Adenosine - analogs & derivatives Adenosine - pharmacology Adenosine - therapeutic use Adenosine A3 Receptor Agonists Adenosine A3 Receptor Antagonists Animals Anti-Inflammatory Agents - pharmacology Anti-Inflammatory Agents - therapeutic use Arthritis, Experimental - drug therapy Arthritis, Experimental - pathology Bacterial arthritis and osteitis Bacterial diseases Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Collagen - immunology Diseases of the osteoarticular system Dose-Response Relationship, Drug Female Human bacterial diseases Infectious diseases Joints - drug effects Joints - immunology Joints - pathology Lymph Nodes - immunology Male Medical sciences Mice Mice, Inbred DBA Miscellaneous. Osteoarticular involvement in other diseases Pharmacology. Drug treatments Quinazolines - pharmacology Rats Receptor, Adenosine A3 - metabolism Spleen - immunology Triazoles - pharmacology Tumor Necrosis Factor-alpha - metabolism |
| title | Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models |
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