Interleukin (IL)-31 induces pro-inflammatory cytokines in human monocytes and macrophages following stimulation with staphylococcal exotoxins.
BACKGROUND
IL-31 is a cytokine expressed by T cells following activation with cytokines or staphylococcal exotoxins. A major function of IL-31 in atopic dermatitis (AD) is the induction of pruritus in the skin via the IL-31 receptor on sensory nerve cells. However, the regulation of the IL-31 receptor and pro-inflammatory functions of IL-31 in human monocytes and monocyte-derived cells are yet to be studied in detail.


OBJECTIVE
To investigate the regulation and function of IL-31 receptors in resting and activated human monocytes, macrophages and dendritic cells.


METHODS
Human monocytes, macrophages and dendritic cells were stimulated with staphylococcal exotoxins (SEB, alpha-toxin) or cytokines (IFN-gamma, IL-13). IL-31RA expression and regulation were then investigated at both the mRNA and the protein level. Subsequently, functional effects of IL-31 stimulation on cytokine secretion were measured at the protein level.


RESULTS
Staphylococcal exotoxins significantly up-regulated IL-31RA expression on monocytes and macrophages but not on dendritic cells at both the mRNA and the protein level. IL-31 enhanced the secretion of IL-1beta, IL-6 and IL-18 and up-regulated CD86 expression. In patients with AD, functional IL-31RA was also detected following stimulation of PBMC with IFN-gamma. However, this was not observed in healthy individuals.


CONCLUSIONS
IL-31 induces pro-inflammatory effects in activated human monocytes and macrophages. This may have implications for cutaneous inflammation in eczema where an over-expression of IL-31 has been described previously. Moreover, our findings provide a new link between staphylococcal colonization and the worsening of inflammation via IL-31. Further therapeutic considerations may include IL-31 as a target in AD.
Kasraie
S
S
Division of Immunodermatology and Allergy Research, Department of Dermatology and Allergy, Hannover Medical School, Ricklinger Strasse 5, Hannover, Germany.
Niebuhr
M
M
Werfel
T
T
D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D003713:Dendritic Cells; D004485:Eczema; D005098:Exotoxins / Q000494:pharmacology*; D006801:Humans; D018836:Inflammation Mediators; D007378:Interleukins / Q000502:physiology*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D018123:Receptors, Interleukin / Q000032:analysis / Q000235:genetics; D013210:Staphylococcus / Q000472:pathogenicity
D016207:Cytokines; D005098:Exotoxins; C502187:IL31 protein, human; C502188:IL31RA protein, human; D018836:Inflammation Mediators; D007378:Interleukins; D012333:RNA, Messenger; D018123:Receptors, Interleukin