Related Experiment Video
Updated: May 28, 2026
11:27
A Guide to Production, Crystallization, and Structure Determination of Human IKK1/α
Published on: November 2, 2018
CCL27 expression is regulated by both p38 MAPK and IKKβ signalling pathways.
Jette Lindorff Riis1, Claus Johansen, Christian Vestergaard
1Department of Dermatology, Aarhus Sygehus, Aarhus University Hospital, Aarhus C, Denmark. jette.lindorff.riis@ki.au.dk
Cytokine
|October 14, 2011
Summary
Interleukin-1 beta (IL-1β) induces skin chemokine CCL27 expression in keratinocytes via p38 MAPK and IKK/NF-κB pathways. This regulation is crucial for inflammatory skin disease pathogenesis.
Area of Science:
- Immunodermatology
- Molecular Biology
- Cell Signaling
Background:
- CCL27, a skin-specific chemokine, promotes lymphocyte migration to the skin via CCR10 binding, contributing to inflammatory skin diseases.
- The precise regulatory mechanisms of CCL27 gene expression remain largely unelucidated.
Purpose of the Study:
- To investigate the regulation of IL-1β-induced CCL27 gene expression in normal human keratinocytes (NHEK).
Main Methods:
- Utilized inhibitors of IκB kinase (IKK) and p38 mitogen-activated protein kinase (MAPK).
- Assessed the impact of downstream kinases MSK1 and Mnk1+2 inhibitors on CCL27 expression.
- Employed electrophoretic mobility shift assay (EMSA) and supershift analyses to identify NF-κB involvement.
Main Results:
- Inhibition of IKK and p38 MAPK significantly reduced CCL27 mRNA and protein expression.
- Downstream kinases MSK1 and Mnk1+2 were implicated in CCL27 regulation.
- EMSA and supershift assays confirmed the binding of p50/p65 NF-κB heterodimers to the CCL27 gene promoter.
Conclusions:
- IL-1β-induced CCL27 gene expression in NHEK is regulated by both the p38 MAPK/MSK1/Mnk1+2 and IKKβ/NF-κB signaling pathways.
- These findings elucidate key molecular mechanisms underlying CCL27 regulation in skin inflammation.
Related Concept Videos
01:07MAPK Signaling Cascades
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
01:19Interactions Between Signaling Pathways
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
02:26NF-κB-dependent Signaling Pathway
The transcription factor NF-κB was discovered in 1986 in the lab of Nobel laureate Professor David Baltimore, for its interaction with the immunoglobulin light chain enhancer in B-cells. After more than three decades of study, it is now evident that NF-κB regulates the expression of over 100 genes. Most of these genes play an essential role in the innate and adaptive immune responses as well as the inflammatory responses of animals.
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
NF-κB-dependent Signaling Mechanism
The heterodimer of NF-κB...
01:20The JAK-STAT Signaling Pathway
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
01:25cAMP-dependent Protein Kinase Pathways
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
02:34Inhibition of Cdk Activity
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...