intrinsic-factor and Inflammation

This article reviews the mediation systems participating or potentially participating in inflammatory disease, especially in immunologic injury of the glomerulus. Mediator systems are separated into 3 mechanisms: the first involves complement and neutrophils; the second involves systems unrelated to neutrophils and complement components from C3 to C9; and the third involves blood monocytes. Major emphasis is given to an analysis of factors that potentially participate in the second mechanism. These include humoral factors such as the coagulation system and Hageman factor systems and cellular factor such as platelets or cells resident in the glomerulus. Studies on a role of vasoactive amines are presented. The importance of separating neutrophil-dependent and -independent mechanisms in these studies is emphasized. A review of current knowledge of the biochemical mechanisms involved in the Hageman factor system is presented because of the potential role of these components in the development of inflammation.

Topics: Animals; Basement Membrane; Complement System Proteins; Factor XII; Fibrin; Fibrinogen; Glomerulonephritis; Immune Complex Diseases; Inflammation; Intrinsic Factor; Kidney Glomerulus; Nephritis; Rabbits; Rats

Topics: Blood Coagulation; Blood Platelets; Complement System Proteins; Disseminated Intravascular Coagulation; Factor VII; Hemostasis; Humans; Inflammation; Intrinsic Factor; Kinins; Mathematics

Skin epidermis constitutes the exterior barrier that protects the body from dehydration and environmental assaults. Barrier defects underlie common inflammatory skin diseases, but the molecular mechanisms that maintain barrier integrity and regulate epidermal-immune cell cross-talk in inflamed skin are not fully understood. In this study, we show that skin epithelia-specific deletion of Ovol1, which encodes a skin disease‒linked transcriptional repressor, impairs the epidermal barrier and aggravates psoriasis-like skin inflammation in mice in part by enhancing neutrophil accumulation and abscess formation. Through molecular studies, we identify IL-33, a cytokine with known pro-inflammatory and anti-inflammatory activities, and Cxcl1, a neutrophil-attracting chemokine, as potential weak and strong direct targets of Ovol1, respectively. Furthermore, we provide functional evidence that elevated Il33 expression reduces disease severity in imiquimod-treated Ovol1-deficient mice, whereas persistent accumulation and epidermal migration of neutrophils exacerbate it. Collectively, our study uncovers the importance of an epidermally expressed transcription factor that regulates both the integrity of the epidermal barrier and the behavior of neutrophils in psoriasis-like inflammation.

Topics: Animals; Dermatitis; Disease Models, Animal; DNA-Binding Proteins; Epidermis; Inflammation; Intrinsic Factor; Keratinocytes; Mice; Neutrophils; Psoriasis; Skin; Transcription Factors