Alternaria-Induced Releases Of IL-1 Alpha and IL-1 Beta From Airway Epithelial Cells Through Syk and PKC Signaling Pathways

Purpose Epidemiologic studies have reported that Asian sand dust (ASD) is associated with chronic inflammatory diseases of the respiratory system. Glucocorticoids (GCs) have potent anti-inflammatory properties. The aims of this study were to evaluate the effects of GCs on ASD-induced interleukin-32 (IL-32) expression and to identify the underlying signaling pathways in airway epithelial cells. Methods A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used to evaluate cytotoxicity in A549 and human primary nasal epithelial cells. Expression levels of IL-32 messenger RNA and protein were measured by Western blot, real-time polymerase chain reaction, ELISA, and immunofluorescence staining. Signaling pathways were analyzed using specific inhibitors of Akt, MAPK, or NF- κB. The effects of GCs on the expression of ASD-induced IL-32 were confirmed with ex vivo organ cultures of the nasal interior turbinate. Results ASD (0–400 ng/mL) had no significant cytotoxic effects in A549 cells and human primary nasal epithelial cells. Expression levels of IL-32 were dose-dependently upregulated by ASD treatment in A549 cells. ASD induced phosphorylation of Akt, MAPK, and NF-κB, whereas GCs and specific inhibitors of Akt, MAPK, and NF-κB downregulated these activations and the expression of IL-32. These findings were further confirmed in human primary nasal epithelial cells and ex vivo organ cultures of the nasal interior turbinate. Conclusions GCs have an inhibitory effect on ASD-induced IL-32 expression via the Akt, MAPK, and NF- κB signaling pathways in airway epithelial cells.

Download Full-text

CXCR3 chemokine receptor-induced chemotaxis in human airway epithelial cells: role of p38 MAPK and PI3K signaling pathways

AJP Cell Physiology ◽

10.1152/ajpcell.00441.2005 ◽

2006 ◽

Vol 291 (1) ◽

pp. C34-C39 ◽

Cited By ~ 60

Author(s):

Syed Shahabuddin ◽

Rong Ji ◽

Ping Wang ◽

Eugene Brailoiu ◽

Na Dun ◽

...

Keyword(s):

Epithelial Cell ◽

Epithelial Cells ◽

Signaling Pathways ◽

P38 Mapk ◽

Chemokine Receptor ◽

Airway Epithelial Cells ◽

Chronic Obstructive ◽

Airway Epithelial ◽

Human Airway ◽

Human Airway Epithelial Cells

Human airway epithelial cells (HAEC) constitutively express the CXC chemokine receptor CXCR3, which regulates epithelial cell movement. In diseases such as chronic obstructive pulmonary disease and asthma, characterized by denudation of the epithelial lining, epithelial cell migration may contribute to airway repair and reconstitution. This study compared the potency and efficacy of three CXCR3 ligands, I-TAC/CXCL11, IP-10/CXCL10, and Mig/CXCL9, as inducers of chemotaxis in HAEC and examined the underlying signaling pathways involved. Studies were performed in cultured HAEC from normal subjects and the 16-HBE cell line. In normal HAEC, the efficacy of I-TAC-induced chemotaxis was 349 ± 88% (mean ± SE) of the medium control and approximately one-half the response to epidermal growth factor, a highly potent chemoattractant. In normal HAEC, Mig, IP-10, and I-TAC induced chemotaxis with similar potency and a rank order of efficacy of I-TAC = IP-10 > Mig. Preincubation with pertussis toxin completely blocked CXCR3-induced migration. Of interest, intracellular [Ca2+] did not rise in response to I-TAC, IP-10, or Mig. I-TAC induced a rapid phosphorylation (5–10 min) of two of the three MAPKs, i.e., p38 and ERK1/2. Pretreatment of HAEC with the p38 inhibitor SB 20358 or the PI3K inhibitor wortmannin dose-dependently inhibited the chemotactic response to I-TAC. In contrast, the ERK1/2 inhibitor U0126 had no effect on chemotaxis. These data indicate that in HAEC, CXCR3-mediated chemotaxis involves a G protein, which activates both the p38 MAPK and PI3K pathways in a calcium-independent fashion.

Download Full-text