Overexpression of CRIP in transgenic mice alters cytokine patterns and the immune response.
Cysteine-rich intestinal protein (CRIP), which contains a double zinc finger motif, is a member of the Group 2 LIM protein family. Our results showed that the developmental regulation of CRIP in neonates was not influenced by conventional vs. specific pathogen-free housing conditions. Thymic and splenic CRIP expression was not developmentally regulated. A line of transgenic (Tg) mice that overexpress the rat CRIP gene was created. When challenged with lipopolysaccharide, the Tg mice lost more weight, exhibited increased mortality, experienced greater diarrhea incidence, and had less serum interferon-gamma (IFN-gamma) and more interleukin (IL)-6 and IL-10. Similarly, splenocytes from the Tg mice produced less IFN-gamma and IL-2 and more IL-10 and IL-6 upon mitogen stimulation. Delayed-type hypersensitivity response was less in the Tg mice. Influenza virus infection produced greater weight loss in the Tg mice, which also showed delayed viral clearance. The observed responses to overexpression of the CRIP gene are consistent with a role for this LIM protein in a cellular pathway that produces an imbalance in cytokine pattern favoring Th2 cytokines.
Lanningham-Foster
Lorraine
L
Food Science and Human Nutrition Department, Center for Nutritional Sciences, University of Florida, Gainesville, Florida 32611, USA.
Green
Calvert L
CL
Langkamp-Henken
Bobbi
B
Davis
Barbara A
BA
Nguyen
Khanh T
KT
Bender
Bradley S
BS
Cousins
Robert J
RJ
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis*; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D007109:Immunity; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis / Q000097:blood; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis / Q000097:blood; D060588:LIM Domain Proteins; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000503:physiopathology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012772:Shock, Septic / Q000276:immunology / Q000503:physiopathology; D013154:Spleen / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology; D013950:Thymus Gland / Q000378:metabolism; D014162:Transfection; D015431:Weight Loss; D015032:Zinc / Q000097:blood
D002352:Carrier Proteins; C489507:Crip1 protein, mouse; C071434:Crip1 protein, rat; D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D060588:LIM Domain Proteins; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma; D015032:Zinc