Publication Date:
2008-02-02
Description:
Cyclin D1 (CyD1) is a pivotal cell cycle-regulatory molecule and a well-studied therapeutic target for cancer. Although CyD1 is also strongly up-regulated at sites of inflammation, its exact roles in this context remain uncharacterized. To address this question, we developed a strategy for selectively silencing CyD1 in leukocytes in vivo. Targeted stabilized nanoparticles (tsNPs) were loaded with CyD1-small interfering RNA (siRNA). Antibodies to beta(7) integrin (beta(7) I) were then used to target specific leukocyte subsets involved in gut inflammation. Systemic application of beta(7) I-tsNPs silenced CyD1 in leukocytes and reversed experimentally induced colitis in mice by suppressing leukocyte proliferation and T helper cell 1 cytokine expression. This study reveals CyD1 to be a potential anti-inflammatory target, and suggests that the application of similar modes of targeting by siRNA may be feasible in other therapeutic settings.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2490797/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2490797/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Peer, Dan -- Park, Eun Jeong -- Morishita, Yoshiyuki -- Carman, Christopher V -- Shimaoka, Motomu -- AI63421/AI/NIAID NIH HHS/ -- HL048675/HL/NHLBI NIH HHS/ -- P01 HL048675-150013/HL/NHLBI NIH HHS/ -- R01 AI063421-04/AI/NIAID NIH HHS/ -- New York, N.Y. -- Science. 2008 Feb 1;319(5863):627-30. doi: 10.1126/science.1149859.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Immune Disease Institute and Department of Anesthesia, Harvard Medical School, 200 Longwood Avenue, Boston, MA 02115, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18239128" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antibodies
;
Cell Proliferation
;
Colitis/*drug therapy/metabolism/pathology
;
Colon/pathology
;
Cyclin D
;
Cyclins/*genetics/physiology
;
Cytokines/metabolism
;
*Drug Carriers
;
*Genes, bcl-1
;
Hyaluronic Acid
;
Inflammatory Bowel Diseases/drug therapy/immunology/pathology
;
Integrin beta Chains/immunology
;
Leukocytes/cytology/*drug effects/immunology/metabolism
;
Liposomes
;
Mice
;
Nanoparticles
;
Protamines
;
*RNA Interference
;
RNA, Messenger/genetics/metabolism
;
RNA, Small Interfering/*administration & dosage/chemistry/metabolism
;
T-Lymphocytes, Helper-Inducer/immunology
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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