Extracellular signal-regulated kinase (ERK)1/2 regulates interleukin (IL)-6 and 8 expression by a novel cytokine, ML-1

Induction of C-X-C Chemokines, Growth-Related Oncogene α Expression, and Epithelial Cell-Derived Neutrophil-Activating Protein-78 by ML-1 (Interleukin-17F) Involves Activation of Raf1-Mitogen-Activated Protein Kinase Kinase-Extracellular Signal-Regulated Kinase 1/2 Pathway

“…Additional time intervals between the 12-and 24-h time points will be needed to identify its release kinetics. Of interest, we have also found previously a similar "delay" phenomenon for ML-1-induced IL-6 secretion (Kawaguchi et al, 2002). The delay in protein expression may be as a result of the required time frame for protein modification and/or transport, or alternatively, but not mutually exclusively, a faster synthesis/secretion kinetic requires an additional factor induced by ML-1.…”

“…Our previous and current data demonstrated that ML-1-induced IL-8, GRO␣, and ENA-78 production is dependent on the activation of ERK1/2, but not p38 and JNK in the MAPK signaling pathway (Kawaguchi et al, 2002). ERK1/2 is known to be involved in the regulation of cell proliferation and apoptosis.…”

“…ML-1 is expressed in activated CD4 ϩ T cells, basophils, and mast cells, three important cell types involved in airway inflammation (Kawaguchi et al, 2001). We have previously shown that ML-1 is able to induce the expression of IL-6, IL-8, and (intercellular adhesion molecule-1 in bronchial epithelial cells (Kawaguchi et al, 2001) and that this activation process is mediated, in part, through the phosphorylation of ERK1/2, but not p38 and Jun-N-terminal kinase (JNK) (Kawaguchi et al, 2002). The importance of MAPKs in controlling cellular response to the environment and in regulating gene expression, cell growth, and apoptosis has made them a priority for research related to many human diseases (English and Cobb, 2002).…”

Induction of granulocyte-macrophage colony-stimulating factor by a new cytokine, ML-1 (IL-17F), via Raf I-MEK-ERK pathway

“…It is of interest to note that the induction of IL-6 and IL-8 by ML-1 is dependent on the activation of ERK1/2, but not p38 and JNK, 19 suggesting that ML-1 is able to induce multiple cytokines via the same signaling pathway. Also, ERK1/2 may serve as a pivotal signaling molecule for IL-17 family members, such as IL-17A and ML-1 (IL-17F), and would be a potential therapeutic target for IL-17 familyassociated airway diseases.…”

IL-17 cytokine family

“…IL-17F has been shown to be able to induce a similar panel of cytokines and chemokines in bronchial epithelial cells and human umbilical vein endothelial cells (HUVECs). [31][32][33] Besides epithelial and endothelial cells, fibroblasts are known to produce neutrophil-activating factors, IL-6 and IL-8, in response to both IL-17A and IL-17F. 9,29 Recent efforts with mouse models have corroborated these in vitro findings and provided further insight into the functional role of these 2 cytokines in vivo.…”