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C. Yu, R. Mahdi, Sr., A. Eseonu, Y. Lee, C.-C. Chan, C. E. Egwuagu; Socs1 Deficient Mice Develop Severe Endotoxin-induced Uveitis (eiu). Invest. Ophthalmol. Vis. Sci. 2009;50(13):2653.
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Endotoxin-induced uveitis (EIU) can be induced in certain animal species including rats, mice and rabbits by subcutaneous injection of a sublethal dose of lipopolysaccharide (LPS). It is a useful model for the study of acute and sub-acute anterior ocular inflammation in humans. Suppressor of cytokine signaling 1 (SOCS1) is a negative feedback regulator of LPS signaling in immune cells and is thought to contribute to mechanisms of LPS resistance. Here, we have used mice deficient in SOCS1 to investigate whether SOCS1 confers protection from developing severe acute anterior uveitis.
SOCS1 deficient mice die by three weeks of age. However the lethal phenotype can be rescued if bred to a STAT1 null background. We therefore generated SOCS1-/-, STAT1-/- double KO (DKO) mice by crossbreeding SOCS1+/- with STAT1-/- mice. For EIU study, two control mouse strains were used: wild type and a STAT1-deficient (STAT1KO) mouse strains. All of the three mouse strains are on a C57bl/6 background and we induced EIU by injecting LPS (300 µg/mouse) into footpads or IP. Eyes were enucleated 1 or 2 days later. Peripheral blood and lymph node cells were analyzed for the expression of cell surface proteins and intracellular cytokines by FACS analysis. RNA isolated from the cornea was analyzed for chemokine expression by RT-PCR.
Compared to wild type mice, EIU was more severe in SOCS1-deficient mice by several folds of magnitude. The disease in SOCS1-deficient mice is characterized by significant elevation of CD14-, F4/80-, CCR5- and CCR6-expressing inflammatory cells in eyes. Furthermore, the chemokine receptors, CCR6 (ligands: LARC and IL-17) and CXCR3 (ligands: MIG and IP10) are elevated while CCR7 is decreased.
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