Related Experiment Video

Updated: Aug 13, 2026

In vitro Measurements of Tracheal Constriction Using Mice
10:20

In vitro Measurements of Tracheal Constriction Using Mice

Published on: June 25, 2012

p38 MAP kinase regulates IL-1 beta responses in cultured airway smooth muscle cells

J D Laporte1, P E Moore, T Lahiri

  • 1Physiology Program, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|October 29, 2000
PubMed

Insights

Interleukin-1 beta triggers airway smooth muscle hyporesponsiveness by increasing COX-2 via p38 MAP kinase. Inhibiting p38 MAP kinase blocks this effect, suggesting a key role in airway inflammation.

Area of Science:

  • Cellular and Molecular Biology
  • Immunology
  • Respiratory Medicine

Background:

  • Interleukin (IL)-1 beta is known to induce cyclooxygenase (COX)-2 expression in human airway smooth muscle (HASM) cells, leading to beta-adrenergic hyporesponsiveness.
  • The precise signaling pathways mediating these effects require further elucidation.

Purpose of the Study:

  • To investigate the role of p38 mitogen-activated protein (MAP) kinase in IL-1 beta-induced COX-2 expression and beta-adrenergic hyporesponsiveness in HASM cells.

Main Methods:

  • HASM cells were treated with IL-1 beta and/or p38 MAP kinase inhibitor (SB-203580).
  • COX-2 expression, prostaglandin E(2) (PGE(2)) release, and nuclear factor binding (AP-1, NF-kappa B) were measured.
  • Beta-adrenergic hyporesponsiveness was assessed by measuring HASM stiffness using magnetic twisting cytometry.

Main Results:

  • IL-1 beta significantly increased p38 MAP kinase phosphorylation and COX-2 expression.
  • The p38 inhibitor SB-203580 markedly reduced IL-1 beta-induced COX-2 expression and PGE(2) release.
  • SB-203580 abolished the IL-1 beta-mediated hyporesponsiveness of HASM cells to isoproterenol.
  • p38 MAP kinase activation was not dependent on AP-1 or NF-kappa B, and NF-kappa B was not required for IL-1 beta-induced COX-2 expression.

Conclusions:

  • p38 MAP kinase is a critical component of the signaling pathway through which IL-1 beta induces COX-2 expression, PGE(2) release, and beta-adrenergic hyporesponsiveness in HASM cells.
  • Targeting the p38 MAP kinase pathway may offer a therapeutic strategy for inflammatory airway diseases characterized by beta-adrenergic hyporesponsiveness.

More Related Videos

Protein Transfection of Mouse Lung04:21

Protein Transfection of Mouse Lung

Published on: May 15, 2013

An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses08:16

An IL-8 Transiently Transgenized Mouse Model for the In Vivo Long-term Monitoring of Inflammatory Responses

Published on: July 7, 2017

Related Concept Videos

Interactions Between Signaling Pathways01:19

Interactions 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...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
MAPK Signaling Cascades01:07

MAPK 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...
TGF - β Signaling Pathway01:16

TGF - β Signaling Pathway

The TGF-β signaling pathway regulates cell growth, differentiation, adhesion, motility, and development. TGF-β ligands that induce TGF-β signaling are synthesized in their latent form. Several proteases or cell surface receptors such as integrins act upon the latent form, releasing the active ligand. There are three types of mammalian TGF-βs: (TGF-β1, TGF-β2, and TGF-β3) that bind as homodimers or heterodimers to TGF-β receptors. The TGF-β receptors are of three kinds RI, RII, and RIII. The RI...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...