, 2004; Kuula et al., 2009). The findings presented in this paper support the therapeutic

usefulness of the nonantibiotic properties of doxycycline in the treatment of chronic inflammatory diseases such as rheumatoid arthritis and periodontal disease, where suppression of interstitial collagenase and 92-kDa gelatinase (gelatinase B) may be beneficial to reduce pathologically excessive degradation of the ECM. It is noteworthy, as shown in this and previous studies (Hanemaaijer et al., 1997), that the inhibition/reduction of MMP-8 and -9 expression and activities by doxycycline and CMTs is not complete, thus allowing these MMPs to carry out the protective actions (McMillan et al., 2004; Sorsa & Golub, 2005; Kuula et al., 2009). Both doxycyclines and chemically modified tetracyclines, when used in conjunction with other chemotherapy agents, CHIR-99021 in vivo may not only lead to more successful periodontal treatments but may reduce the risks for other significant medical conditions including diabetes, heart attack, stroke and other CVDs (Golub et al., 2009; Payne et al., 2009). This study was supported by grant no. A43273 from the New York State Office of Science, Technology and Academic Research

(NYSTAR), through NYSTAR’s Center of Advanced Technology, Stony Brook University. The authors would like to acknowledge Dr Mary Truhlar, Chair of Department of General Dentistry, Stony Brook University, for her support and encouragement of this project. “
“The complement system is regulated

by inhibitors such as factor see more I (FI), a serine protease that degrades activated complement factors C4b and C3b in the presence of specific cofactors. Mutations and polymorphisms Dipeptidyl peptidase in FI and its cofactors are associated with atypical hemolytic uremic syndrome (aHUS). All 14 complementfactor I mutations associated with aHUS analyzed in this study were heterozygous and generated premature stop codons (six) or amino acid substitutions (eight). Almost all of the mutants were expressed by human embryonic kidney 293 cells but only six mutants were secreted into the medium, three of which were at lower levels than WT. The remaining eight mutants were not secreted but sensitive to deglycosylation with endoglycosidase H, indicating that they were retained early in the secretory pathway. Six secreted mutants were purified and five of them were functionally altered in degradation of C4b/C3b in the fluid-phase in the presence of various cofactors and on endothelial cells. Three mutants cleaved surface-bound C3b less efficiently than WT. The D501N mutant was severely impaired both in solution and on surface irrespective of the cofactor used. In conclusion, mutations in complement factor I affect both secretion and function of FI, which leads to impaired regulation of the complement system in aHUS. Hemolytic uremic syndrome (HUS) is characterized by microangiopathic hemolytic anemia, thrombocytopenia and acute renal failure 1.