Data from: IL-13 and IL-17A activate β1 integrin through an NF-kB/Rho kinase/PIP5K1γ pathway to enhance force transmission in airway smooth muscle

Integrin activation resulting in enhanced adhesion to the extracellular
matrix plays a key role in fundamental cellular processes. Although
integrin activation has been extensively studied in circulating cells such
as leukocytes and platelets, much less is known about the regulation and
functional impact of integrin activation in adherent cells such as smooth
muscle. Here, we show that two different asthmagenic cytokines, IL-13 and
IL-17A, activate type I and IL-17 cytokine receptor families,
respectively, to enhance adhesion of airway smooth muscle. These cytokines
also induce activation of β1 integrins detected by the
conformation-specific antibody HUTS-4. Moreover, HUTS-4 binding is
increased in the smooth muscle of patients with asthma compared to
nonsmokers without lung disease, suggesting a disease-relevant role for
integrin activation in smooth muscle. Indeed, integrin activation induced
by the β1-activating antibody TS2/16, the divalent cation manganese, or
the synthetic peptide β1-CHAMP that forces an extended-open integrin
conformation dramatically enhances force transmission in smooth muscle
cells and airway rings even in the absence of cytokines. We demonstrate
that cytokine-induced activation of β1 integrins is regulated by a common
pathway of NF-κB-mediated induction of RhoA and its effector Rho kinase,
which in turn stimulates PIP5K1γ-mediated synthesis of PIP 2 at focal
adhesions, resulting in β1 integrin activation. Taken together, these data
identify a pathway by which type I and IL-17 cytokine receptor family
stimulation induces functionally relevant β1 integrin activation in
adherent smooth muscle and help to explain the exaggerated force
transmission that characterizes chronic airway diseases such as asthma.