Caspase-11 is not necessary for chemotherapy-induced intestinal mucositis.
Mucositis is a common, dose-limiting toxicity associated with drug and radiation therapy for cancer. The ulcerative lesions of mucositis serve as systemic portals of entry for the micro-organisms that inhabit the mucosa of the gastrointestinal tract and the oral cavity, often leading to systemic infection. The pathogenesis of mucositis is complex, and consists of varying, sequential interactions between pro-inflammatory cytokines, transcription factors, and pro-apoptotic pathways of the mucosal epithelium and the cells and tissues within the submucosa. A possible mechanism for mucositis injury is the activation of caspases, a family of cysteine proteases. Caspase-11, one of 14 members of this enzymatic family, was studied to determine its role in the development of intestinal mucositis after exposure to melphalan in caspase-11 wild-type (+/+) and knockout (-/-) mice. Immunoblots demonstrated the activation of caspase-11 in duodenal and jejunal samples 24 and 48 h after melphalan administration. No significant differences in the level of intestinal cell death or macrophage infiltration, as measured by TUNEL staining and immunohistochemistry, were present between wildtype (+/+) and knockout (-/-) mice. These findings suggest that while caspase-11 activation occurs in response to melphalan, it does not have a primary role in the pathogenesis of intestinal mucositis.
Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Shin-Jung
SJ
Kang
Rishi
R
Popat
Christopher
C
Bragdon
Kathryn
K
Odonnell
Sally
S
Phelan
Junying
J
Yuan
Stephen T
ST
Sonis
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D053471:Caspases, Initiator; D004195:Disease Models, Animal; D005767:Gastrointestinal Diseases / Q000139:chemically induced*; D015151:Immunoblotting; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000209:etiology / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism; D008558:Melphalan / Q000009:adverse effects* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout
D000970:Antineoplastic Agents; C101136:Casp4 protein, mouse; D020169:Caspases; D053471:Caspases, Initiator; D008558:Melphalan