Interleukin (IL)-4 induces production of cytokine-induced neutrophil chemoattractants (CINCs) and intercellular adhesion molecule (ICAM)-1 in lungs of asthmatic rats

Abstract

The present study aimed to examine the effect of interleukin (IL)-4 on neutrophil chemotaxis in airway inflammation in asthmatic rats and the possible mechanism. Male Wistar rats were intranasally instilled with recombinant rat (rr) IL-4 (rrIL-4) at different doses [2, 4 or 8 μg/animal, dissolved in 200 μL normal saline (NS)] or rrIL-4 at 4 μg/animal (dissolved in 200 μL NS). NS (200 μL) and LPS (6 mg/kg/animal, dissolved in 200 μL NS) were intranasally given respectively in the negative and positive control groups. Moreover, the asthmatic lung inflammation was induced in rats which were then intranasally treated with rrIL-4 (4 μg/animal) or LPS (6 mg/kg/animal). The normal rats treated with different doses of rrIL-4 and those asthmatic rats were sacrificed 6 h later. And animals instilled with rrIL-4 at 4 μg were sacrificed 6, 12 or 24 h later. The bronchoalveolar lavage fluid (BALF) and lungs were harvested for detection of leukocyte counts by Wright-Giemsa staining and lung histopathology by haematoxylin-eosin (HE) staining. The levels of cytokine-induced neutrophil chemoattractant (CINC)-1 and intercellular adhesion molecule (ICAM)-1 in BALF were determined by ELISA. Real-time PCR was used to measure the mRNA expression of CINCs (CINC-1, CINC-2α, CINC-2β, CINC-3) and ICAM-1 in lung tissues. The results showed that the intranasal instillation of IL-4 did not induce a recruitment of neutrophils in BALF in rats. However, IL-4 could increase the CINC-1 level in BALF in a dose-dependent manner at 6 h. But the mRNA expression levels of CINC-1, CINC-2α, CINC-2β, CINC-3 were not significantly increased in lungs of IL-4-treated rats relative to NS negative control group. Moreover, IL-4 was found to augment the mRNA expression of ICAM-1 in lungs and the ICAM-1 level in BALF at 6 h. However, the increase in CINC-1 and ICAM-1 levels in BALF of IL-4-treated asthmatic rats was not significantly different from that in untreated asthmatic rats. These findings indicate that IL-4 does not directly recruit neutrophils in the rat lungs, but it may contribute to airway neutrophilia through up-regulation of CINC-1 and ICAM-1.

Novel Mechanisms of Sildenafil in Pulmonary Hypertension Involving Cytokines/Chemokines, MAP Kinases and Akt

“…Among them, CINC-1 and CINC-2α/β have neutrophil chemotactic activity and promote neutrophil-facilitated cell damage in the lungs [32], [33]. In previous studies using an acute lung injury model, serum CINC-1 levels correlated with the elevated lung CINC-1 levels suggesting that circulating CINC-1 levels could be used as an early marker for the subsequent development of organ inflammation and injury [34].…”

In vivo lung perfusion rehabilitates sepsis-induced lung injury

“…34 Endothelial adhesion molecules play a critical roll in LPS-induced lung injury allowing transmigration of inflammatory cells. 35 This up regulation of adhesion molecules attracts neutrophils and lymphocytes, further amplifying the inflammatory cascade through release of additional chemo-attractants. Thus the protein expression of VCAM-1 and ICAM-1 were measured in lung tissue as further indicators of vascular inflammation.…”

Regulatory effect of cytokine-induced neutrophil chemoattractant, epithelial neutrophil-activating peptide 78 and pyrrolidine dithiocarbamate on pulmonary neutrophil aggregation mediated by nuclear factor-κB in lipopolysaccharide-induced acute respiratory distress syndrome mice

“…CINC, a member of the IL-8 family, is a specific PMN chemokine (11). CINC-1 and -3 serve important roles in PMN recruitment to the lung in ARDS induced by LPS (10). The enhanced expression of CINC mRNA and protein inhibits PMN apoptosis and activates a large number of PMNs, causing them to accumulate in the lung and result in lung injury (11).…”

“…Adhesion molecules and their ligands provide a strong adhesion between PMNs and endothelial cells, allowing PMNs to migrate to the vessel wall (8,9). Cytokine-induced neutrophil chemoattractant (CINC), a member of the IL-8 family, is a specific PMN chemokine that serves a crucial function in the aggregation of PMNs in lung tissue (10,11). Nuclear factor-κB (NF-κB) is a critical nuclear transcription factor, able to activate the transcription of a number of inflammatory cytokine genes and regulate the inflammatory response and immunoreaction (12).…”