Antimicrobial peptides are highly conserved evolutionarily and are thought to play an important role in innate immunity at intestinal mucosal surfaces. To better understand the role of the antimicrobial peptide human cathelicidin LL-37/human cationic antimicrobial protein 18 (hCAP18) in intestinal mucosal defense, we characterized the regulated expression and production of this peptide by human intestinal epithelium. LL-37/hCAP18 is shown to be expressed within epithelial cells located at the surface and upper crypts of normal human colon. Little or no expression was seen within the deeper colon crypts or within epithelial cells of the small intestine. Paralleling its expression in more differentiated epithelial cells in vivo, LL-37/hCAP18 mRNA and protein expression was upregulated in spontaneously differentiating Caco-2 human colon epithelial cells and in HCA-7 human colon epithelial cells treated with the cell differentiation-inducing agent sodium butyrate. LL-37/hCAP18 expression by colon epithelium does not require commensal bacteria, since LL-37/hCAP18 is produced with a similar expression pattern by epithelial cells in human colon xenografts that lack a luminal microflora. LL-37/hCAP18 mRNA was not upregulated in response to tumor necrosis factor alpha, interleukin 1␣ (IL-1␣), gamma interferon, lipopolysaccharide, or IL-6, nor did the expression patterns and levels of LL-37/hCAP18 in the epithelium of the normal and inflamed colon differ. On the other hand, infection of HCA-7 cells with Salmonella enterica serovar Dublin or enteroinvasive Escherichia coli modestly upregulated LL-37/hCAP18 mRNA expression. We conclude that differentiated human colon epithelium expresses LL-37/ hCAP18 as part of its repertoire of innate defense molecules and that the distribution and regulated expression of LL-37/hCAP18 in the colon differs markedly from that of other enteric antimicrobial peptides, such as defensins.Antimicrobial peptides and proteins play an important role in innate host defense, and this may be particularly important at mucosal surfaces that form the initial barrier between the host and the external environment (3, 18). Cathelicidins are a family of antimicrobial peptides found in many mammalian species (20). The cathelicidins contain a conserved cathelin domain and a C-terminal domain that varies among species, yielding multiple different antimicrobial peptides (22). LL-37 is the only cathelicidin described thus far in humans. Like other cathelicidins, LL-37 is synthesized as a precursor, termed human cationic antimicrobial protein 18 (hCAP18). The precursor is cleaved to the mature peptide LL-37 by a serine protease, protease-3, in neutrophils after exocytosis (45), although it is not known whether the same processing mechanism operates in other cells.LL-37, alone and in synergy with other antimicrobial proteins (e.g., lactoferrin and lysozyme), has a broad range of bactericidal activities against gram-positive and gram-negative bacteria (2,4,47). In addition, LL-37 can bind to and neutralize bacterial...

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We performed an immunohistochemistry study of the normal human bladder so as to understand the interactions of extracellular matrix (ECM) components and the integrins of cell adhesion that accommodate the volume changes and maintain an impermeable barrier to reabsorption of urine in the bladder. The normal human urothelial cell and/or its plasma membrane contained integrins 0~3, c~V, [31, and [34 but did not contain integrin [33. The urothelial basement membrane (UBM) contained collagen type IV and laminin. Fibronectin and integrins (x3 and [~4 were found in or near the U B M area, with types I and III collagen and tenascin abutting the area. The patterns of collagen, laminin, tenascin, vitronectin, fobronectin, and the 0~3, c~V, [31, and [33 integrins in the lamina propria, vessels, nerves, and smooth-muscle layers are described. These findings detail the normal anatomical ECM/integrin relationship that provides the cellular basis for bladder-wall relationships responsible for its impermeable state and other functions.The relationship of the cellular adhesion mechanisms that help secure the urothelial cells to one another as well as to the underlying urothelial basement membrane (UBM) and extracellular matrix (ECM) components would be expected to contribute to the integrity of the impermeable bladder surface. This adhesion involves a family of celladhesion receptors called integrins, heterodimeric molecules expressed on cell surfaces [3]. The family is composed of at least 13 c~ chains and 8 [3 chains which, depending upon pairing, form heterodimers that recognize one or more ligands present on E C M or on opposing cell surfaces. Only limited information is known about the nature of the integrins or their E C M ligands that perform as the adhesion molecules in the bladder wall.The bladder wall of patients with interstitial cystitis, as characterized by varying degrees of chronic inflammaCorrespondence to: