Interleukin-1 and Cutaneous Inflammation: A Crucial Link Between Innate and Acquired Immunity

Abstract

As our primary interface with the environment, the skin is constantly subjected to injury and invasion by pathogens. The fundamental force driving the evolution of the immune system has been the need to protect the host against overwhelming infection. The ability of T and B cells to recombine antigen receptor genes during development provides an efficient, flexible, and powerful immune system with nearly unlimited specificity for antigen. The capacity to expand subsets of antigen-specific lymphocytes that become activated by environmental antigens (memory response) is termed "acquired" immunity. Immunologic memory, although a fundamental aspect of mammalian biology, is a relatively recent evolutionary event that permits organisms to live for years to decades. "Innate" immunity, mediated by genes that remain in germ line conformation and encode for proteins that recognize conserved structural patterns on microorganisms, is a much more ancient system of host defense. Defensins and other antimicrobial peptides, complement and opsonins, and endocytic receptors are all considered components of the innate immune system. None of these, however, are signal-transducing receptors. Most recently, a large family of cell surface receptors that mediate signaling through the NF-kappaB transcription factor has been identified. This family of proteins shares striking homology with plant and Drosophila genes that mediate innate immunity. In mammals, this family includes the type I interleukin-1 receptor, the interleukin-18 receptor, and a growing family of Toll-like receptors, two of which were recently identified as signal-transducing receptors for bacterial endotoxin. In this review, we discuss how interleukin-1 links the innate and acquired immune systems to provide synergistic host defense activities in skin.

The pathophysiology of photosensitivity in lupus erythematosus

“…Like TNF-a, IL-1 has broad pro-inflammatory activities (209). IL-1a predominates in keratinocytes, while IL-1b is the predominant form in monocytes, macrophages and dendritic cells.…”

Dermatitis due to epiregulin deficiency and a critical role of epiregulin in immune-related responses of keratinocyte and macrophage

“…A bioactive transmembrane precursor, pro-HB-EGF, was suggested to induce growth inhibition or apoptosis rather than the proliferative response induced by soluble HB-EGF (10). EP (11-17) acts as an autocrine growth factor in normal human keratinocytes in vitro (15); however, its physiological role in vivo still remains to be elucidated.Keratinocytes in the epidermis play critical roles in the cutaneous immune-related responses (18) and contain biologically active IL-1␣ (19), which is released to extracellular space upon damage and is a major player in skin inflammation (20). Overexpression of IL-1␣ in murine epidermis produces inflammatory skin lesions, indicating the critical role of IL-1␣ in skin inflammation (21).…”

Regulation of Interleukin-1α Expression by Integrins and Epidermal Growth Factor Receptor in Keratinocytes from a Mouse Model of Inflammatory Skin Disease

“…Keratinocyte-derived IL-1 is known to be an important initiator of wound healing in response to skin injury (6,7). Disruption of the epidermis causes the release of pre-formed pools of IL-1 (8,9), which, through stimulation of endothelial and immune cells, can generate an inflammatory infiltrate at the site of injury (7,10).…”

“…Disruption of the epidermis causes the release of pre-formed pools of IL-1 (8,9), which, through stimulation of endothelial and immune cells, can generate an inflammatory infiltrate at the site of injury (7,10). Keratinocytes themselves are activated by the released IL-1; they become more migratory and express keratins associated with a hyperproliferative state (11,12).…”