Send to

Choose Destination
Am J Physiol Lung Cell Mol Physiol. 2009 Jul;297(1):L26-34. doi: 10.1152/ajplung.00026.2009. Epub 2009 Apr 24.

Effect of proinflammatory cytokines on regulation of sarcoplasmic reticulum Ca2+ reuptake in human airway smooth muscle.

Author information

Departments of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.


Airway inflammation leads to increased intracellular Ca(2+) ([Ca(2+)](i)) levels in airway smooth muscle (ASM) cells. Sarcoplasmic reticulum Ca(2+) release and reuptake are key components of ASM [Ca(2+)](i) regulation. Ca(2+) reuptake occurs via sarcoendoplasmic reticulum Ca(2+) ATPase (SERCA) and is regulated by the inhibitory protein phospholamban (PLB) in many cell types. In human ASM, we tested the hypothesis that inflammation increases PLB, thus inhibiting SERCA function, and leading to maintained [Ca(2+)](i) levels. Surprisingly, we found that human ASM does not express PLB protein (although mRNA is detectable). Overnight exposure to the proinflammatory cytokines TNFalpha and IL-13 did not induce PLB expression, raising the issue of how SERCA is regulated. We then found that direct SERCA phosphorylation (via CaMKII) occurs in human ASM. In fura-2-loaded human ASM cells, we found that the CaMKII antagonist KN-93 significantly slowed the rate of fall of [Ca(2+)](i) transients induced by ACh or bradykinin (in zero extracellular Ca(2+)), suggesting a role for CaMKII-mediated SERCA regulation. SERCA expression was decreased by cytokine exposure, and the rate of fall of [Ca(2+)](i) transients was slowed in cells exposed to TNFalpha and IL-13. Cytokine effects on Ca(2+) reuptake were unaffected by additional exposure to KN-93. These data indicate that in human ASM, SERCA is regulated by mechanisms such as CaMKII and that airway inflammation maintains [Ca(2+)](i) levels by decreasing SERCA expression and slowing Ca(2+) reuptake.

Comment in

[Indexed for MEDLINE]
Free PMC Article

Publication types, MeSH terms, Substances, Grant support

Publication types

MeSH terms


Grant support

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center