| Caspase-1 modulates incisional sensitization and inflammation. | |
| | |
MedLine Citation:
|
PMID: 20823759 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
BACKGROUND: Surgical injury induces production and release of inflammatory mediators in the vicinity of the wound. They in turn trigger nociceptive signaling to produce hyperalgesia and pain. Interleukin-1β plays a crucial role in this process. The mechanism regulating production of this cytokine after incision is, however, unknown. Caspase-1 is a key enzyme that cleaves prointerleukin-1β to its active form. We hypothesized that caspase-1 is a crucial regulator of incisional interleukin-1β levels, nociceptive sensitization, and inflammation. METHODS: These studies employed a mouse hind paw incisional model. Caspase-1 was blocked using the selective inhibitors Ac-YVAD-CMK and VRTXSD727. Nociceptive sensitization, edema, and hind paw warmth were followed in intact animals whereas caspase-1 activity, cytokine, and prostaglandin E2 levels were assessed in homogenized skin. Confocal microscopy was used to detect the expression of caspase-1 near the wounds. RESULTS: Analysis of enzyme activity demonstrated that caspase-1 activity was significantly increased in periincisional skin. Pretreatment with Ac-YVAD-CMK significantly reduced mechanical allodynia and thermal hyperalgesia. Repeated administration of this inhibitor produced robust analgesia, especially to mechanical stimulation. Administration of VRTXSD727 provided qualitatively similar results. Caspase-1 inhibition also reduced edema and the normally observed increase in paw warmth around the wound site. Correspondingly, caspase-1 inhibition significantly reduced interleukin-1β as well as macrophage-inflammatory protein 1α, granulocyte colony-stimulating factor, and prostaglandin E2 levels near the wound. The expression of caspase-1 was primarily observed in keratinocytes in the epidermal layer and in neutrophils deeper in the wounds. CONCLUSIONS: The current study demonstrates that the inhibition of caspase-1 reduces postsurgical sensitization and inflammation, likely through a caspase-1/interleukin-1β-dependent mechanism. |
| | |
Authors:
|
De-Yong Liang; XiangQi Li; Wen-Wu Li; Dennis Fiorino; Yanli Qiao; Peyman Sahbaie; David C Yeomans; J David Clark |
Related Documents
:
|
7774869 - Local regulation of extracellular matrix structure. 16622849 - Matrix metalloproteinases and cellular motility in development and disease. 18619669 - Progress in matrix metalloproteinase research. 2688809 - Growth factors in embryogenesis. 18829709 - Proteomic analysis of scleroderma lesional skin reveals activated wound healing phenoty... 19204729 - Dynamic expression of epidermal caspase 8 simulates a wound healing response. 10953979 - Generation of dendritic cells from human chronic myelomonocytic leukemia cells in fetal... 7774869 - Local regulation of extracellular matrix structure. 19494279 - The t cell stat signaling network is reprogrammed within hours of bacteremia via second... |
Publication Detail:
|
Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
|
Title: Anesthesiology Volume: 113 ISSN: 1528-1175 ISO Abbreviation: Anesthesiology Publication Date: 2010 Oct |
Date Detail:
|
Created Date: 2010-09-24 Completed Date: 2010-10-13 Revised Date: 2012-05-07 |
Medline Journal Info:
|
Nlm Unique ID: 1300217 Medline TA: Anesthesiology Country: United States |
Other Details:
|
Languages: eng Pagination: 945-56 Citation Subset: AIM; IM |
Affiliation:
|
Department of Anesthesiology, Veterans Affairs Palo Alto Health Care System, Palo Alto, California, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Biological Markers Body Temperature / drug effects Caspase 1 / antagonists & inhibitors, physiology* Chemokine CCL3 / metabolism Dinoprostone / metabolism Edema / pathology Granulocyte Colony-Stimulating Factor / cerebrospinal fluid Hindlimb / pathology Hot Temperature Hyperalgesia / physiopathology Immunohistochemistry Inflammation / metabolism, pathology* Interleukin-1beta / metabolism Male Mice Mice, Inbred BALB C Pain / psychology Pain Measurement Pain Threshold / physiology Skin / metabolism Surgical Procedures, Operative / adverse effects* |
| Grant Support | |
ID/Acronym/Agency:
|
GM079126/GM/NIGMS NIH HHS; R01 GM079126-02S1/GM/NIGMS NIH HHS; R01 GM079126-04/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Biological Markers; 0/Ccl3 protein, mouse; 0/Chemokine CCL3; 0/Interleukin-1beta; 143011-72-7/Granulocyte Colony-Stimulating Factor; 363-24-6/Dinoprostone; EC 3.4.22.36/Caspase 1 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: The American Society of Anesthesiologists Closed Claims Project: The Beginning.
Next Document: Neurally Adjusted Ventilatory Assist in Critically Ill Postoperative Patients: A Crossover Randomize...