Related Experiment Video

Updated: May 25, 2026

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice
06:40

Cecal Ligation and Puncture-induced Sepsis as a Model To Study Autophagy in Mice

Published on: February 9, 2014

Map kinase phosphatase 5 protects against sepsis-induced acute lung injury

Feng Qian1, Jing Deng, Benjamin N Gantner

  • 1Dept. of Pharmacology, Univ. of Illinois at Chicago, Chicago, IL 60612, USA. fengqian@uic.edu

American Journal of Physiology. Lung Cellular and Molecular Physiology
|February 7, 2012
PubMed

Insights

Mitogen-activated protein kinase phosphatase 5 (MKP5) is vital for controlling inflammation. MKP5 deficiency exacerbates acute lung injury by increasing inflammatory responses in macrophages and lung tissue.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Mitogen-activated protein kinases (MAPKs) are key regulators of inflammatory processes.
  • While MAPK activation is well-studied, their inactivation mechanisms remain less understood.
  • MAPK phosphatase 5 (MKP5) dephosphorylates and inactivates activated MAPKs.

Purpose of the Study:

  • To investigate the role of MKP5 in regulating inflammatory responses, specifically in the context of sepsis-induced acute lung injury.
  • To determine the impact of MKP5 deficiency on MAPK activation and inflammatory mediator production in macrophages.
  • To assess the contribution of MKP5-deficient macrophages to lung inflammation.

Main Methods:

  • Utilized a mouse model lacking MKP5 (MKP5-deficient mice) and wild-type (WT) controls.
  • Administered lipopolysaccharide (LPS) challenge to induce sepsis-related acute lung injury.
  • Analyzed lung tissue for damage, neutrophil infiltration, and edema.
  • Assessed inflammatory factor production (cytokines, nitric oxide, superoxide) in MKP5-deficient and WT macrophages.
  • Measured MAPK phosphorylation (p38, JNK, ERK) in response to LPS.
  • Performed adoptive transfer experiments using MKP5-deficient and WT macrophages.

Main Results:

  • Mice lacking MKP5 exhibited severe lung tissue damage, increased neutrophil infiltration, and edema after LPS challenge compared to WT mice.
  • MKP5-deficient macrophages produced significantly higher levels of inflammatory cytokines, nitric oxide, and superoxide upon LPS stimulation.
  • LPS stimulation led to enhanced phosphorylation of p38 MAPK, JNK, and ERK in MKP5-deficient macrophages.
  • Adoptive transfer of MKP5-deficient macrophages worsened lung inflammation compared to WT macrophages, indicating their direct contribution.

Conclusions:

  • MKP5 plays a critical protective role in preventing sepsis-induced acute lung injury.
  • MKP5 is essential for the homeostatic regulation of MAPK activation during inflammatory responses.
  • MKP5 deficiency in macrophages leads to heightened inflammatory mediator production and exacerbates lung injury.

More Related Videos

Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation11:07

Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation

Published on: July 6, 2019

Related Concept Videos

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...
PI3K/mTOR/AKT Signaling Pathway01:22

PI3K/mTOR/AKT Signaling Pathway

The mammalian target of rapamycin  (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1  (mTORC1) and mTOR complex 2  (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast,  mTORC2 consists of a rapamycin-insensitive companion...
The JAK-STAT Signaling Pathway01:20

The 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...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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...
cAMP-dependent Protein Kinase Pathways01:25

cAMP-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,...