PMID- 12140176 OWN - NLM STAT- MEDLINE DCOM- 20020828 LR - 20190727 IS - 0041-008X (Print) IS - 0041-008X (Linking) VI - 182 IP - 2 DP - 2002 Jul 15 TI - Differential regulation of epidermal langerhans cell migration by interleukins (IL)-1alpha and IL-1beta during irritant- and allergen-induced cutaneous immune responses. PG - 126-35 AB - Tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, and IL-18 are all known to contribute to the regulation of epidermal Langerhans cells (LC) migration and the subsequent accumulation of dendritic cells (DC) in draining lymph nodes following skin sensitization. However, the cytokine signals that control these responses following skin irritation have yet to be defined. We demonstrate that IL-1alpha, a cytokine associated with skin injury and inflammation, is able to stimulate the activation and migration from the epidermis of LC and their subsequent accumulation in skin-draining lymph nodes. Stimulation of these responses by IL-1alpha required the local availability of TNF-alpha. Using specific neutralizing antibodies, LC migration induced following skin sensitization with oxazolone (Ox) was found to be dependent upon IL-1beta and independent of a requirement for IL-1alpha. However, the converse was true following stimulation of responses with the nonsensitizing skin irritant sodium lauryl sulfate (SLS). Here, the loss of LC from the epidermis and the accumulation of DC in draining lymph nodes required IL-1alpha and not IL-1beta. Despite utilizing different IL-1 isoforms for LC mobilization, the phenotypic characteristics of DC arriving in draining lymph nodes in response to Ox and SLS were similar with respect to the membrane determinants MHC class II, B7-1, B7-2, and intercellular adhesion molecule-1. These data suggest that contact sensitization and skin irritation employ subtly different cytokine networks in the regulation of LC migration, both involving TNF-alpha but demonstrating differential requirements for IL-1 cytokines. The proposal is that different forms of cutaneous trauma may achieve LC migration through distinct molecular mechanisms. FAU - Cumberbatch, Marie AU - Cumberbatch M AD - Syngenta Central Toxicology Laboratory, Alderley Park, Macclesfield, Cheshire, SK10 4TJ, United Kingdom. Marie.Cumberbatch@Syngenta.com FAU - Dearman, Rebecca J AU - Dearman RJ FAU - Groves, Richard W AU - Groves RW FAU - Antonopoulos, Christos AU - Antonopoulos C FAU - Kimber, Ian AU - Kimber I LA - eng PT - Journal Article PL - United States TA - Toxicol Appl Pharmacol JT - Toxicology and applied pharmacology JID - 0416575 RN - 0 (Adjuvants, Immunologic) RN - 0 (Allergens) RN - 0 (Interleukin-1) RN - 0 (Irritants) RN - 0 (Tumor Necrosis Factor-alpha) RN - 15646-46-5 (Oxazolone) SB - IM MH - Adjuvants, Immunologic/pharmacology MH - Allergens/*pharmacology MH - Animals MH - Cell Movement/*physiology MH - Cell Separation MH - Dendritic Cells/drug effects MH - Dermatitis, Contact/*immunology MH - Epidermal Cells MH - Epidermis/drug effects MH - Flow Cytometry MH - In Vitro Techniques MH - Interleukin-1/*pharmacology MH - Irritants/*pharmacology MH - Langerhans Cells/*physiology MH - Lymph Nodes/cytology/drug effects MH - Mice MH - Mice, Inbred BALB C MH - Oxazolone/pharmacology MH - Phenotype MH - Tumor Necrosis Factor-alpha/pharmacology EDAT- 2002/07/26 10:00 MHDA- 2002/08/29 10:01 CRDT- 2002/07/26 10:00 PHST- 2002/07/26 10:00 [pubmed] PHST- 2002/08/29 10:01 [medline] PHST- 2002/07/26 10:00 [entrez] AID - S0041008X02994421 [pii] AID - 10.1006/taap.2002.9442 [doi] PST - ppublish SO - Toxicol Appl Pharmacol. 2002 Jul 15;182(2):126-35. doi: 10.1006/taap.2002.9442.