The interleukin-1 axis and cutaneous inflammation.
Since the discovery that epidermal cell-derived thymocyte-activating factor was identical to interleukin (IL)-1 alpha and -beta in 1986, these molecules have been implicated in the pathogenesis of skin diseases. In 1995, it has become clear that a group of gene products function to regulate the activity of IL-1. IL-1 alpha and mature 17-kD IL-1 beta (cleaved from precursor by IL-1 beta-converting enzyme) bind to the type 1 IL-1 receptor to transduce a signal. This process can be antagonized at the level of the receptor by two distinct forms of the IL-1 receptor antagonist, which bind to the type I receptor but do not transduce a signal. The process can also be antagonized at the level of the ligand by either cell-bound or soluble type 2 IL-1 receptor. This type 2 IL-1 receptor binds ligand but does not transduce a signal. Keratinocytes can make each of these variables in vitro, and the balance between agonists and antagonists dictates the biologic outcome of a putative IL-1-mediated event. Transgenic mice that overexpress each of these factors individually in epidermis will be useful for enhancing our understanding of the cutaneous biology of IL-1.
Kupper
T S
TS
Division of Dermatology, Harvard Skin Disease Research Center, Harvard Medical School, Boston, Massachusetts 02115, USA.
Groves
R W
RW
D000818:Animals; D016207:Cytokines / Q000502:physiology; D003872:Dermatitis / Q000503:physiopathology*; D006801:Humans; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000737:chemistry / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D017472:Receptors, Interleukin-1 / Q000502:physiology; D011994:Recombinant Proteins; D012795:Sialoglycoproteins / Q000502:physiology
D016207:Cytokines; C507763:IL1RN protein, human; C507764:Il1rn protein, mouse; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D012795:Sialoglycoproteins