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Interleukin (IL)-4 induces leukocyte infiltration in vivo by an indirect mechanism.

Ratthé C, Ennaciri J, Garcês Gonçalves DM, Chiasson S, Girard D - Mediators Inflamm. (2009)

Bottom Line: The IL-4-induced expression of CCL-2 was confirmed by ELISA.Air pouch resident lining cells were harvested and were found to express IL-4Ralpha.CCL2 mRNA expression was monitored in lining cells, cells isolated from the air pouch skin, in RAW264.7 macrophage and in epithelial Mode-K cells and its expression was increased in response to IL-4 in all conditions.

View Article: PubMed Central - PubMed

Affiliation: INRS-Institut Armand-Frappier, Université du Québec, Québec, Canada.

ABSTRACT
Interleukin (IL)-4 is a cytokine known mainly for its anti-inflammatory activity. Using the in vivo murine air pouch model, we found that IL-4 significantly increased the number of leukocytes after 9 hours of treatment, consisting mainly of neutrophil (60%) and monocytic (40%) cell populations. Using an antibody array, we found that the expression of several analytes (predominantly CCL2) was increased by IL-4 before the arrival of leukocytes. The IL-4-induced expression of CCL-2 was confirmed by ELISA. Air pouch resident lining cells were harvested and were found to express IL-4Ralpha. CCL2 mRNA expression was monitored in lining cells, cells isolated from the air pouch skin, in RAW264.7 macrophage and in epithelial Mode-K cells and its expression was increased in response to IL-4 in all conditions. We conclude that IL-4 can attract leukocytes in vivo by an indirect mechanism involving the production of several analytes by, at least, resident cells.

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IL-4 induces inflammation in vivo. Murine air pouches were raised before injection of buffer (Ctrl) or 250 ng/ml IL-4 and exudates were harvested at the indicated periods of time and the number of leukocytes was calculated. Results are means ± SEM (n ≥ 6). *P < .05 versus Ctrl.
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fig1: IL-4 induces inflammation in vivo. Murine air pouches were raised before injection of buffer (Ctrl) or 250 ng/ml IL-4 and exudates were harvested at the indicated periods of time and the number of leukocytes was calculated. Results are means ± SEM (n ≥ 6). *P < .05 versus Ctrl.

Mentions: Previous studies demonstrated that IL-4 induces chemoattraction of different cell types such as eosinophils, macrophages, fibroblasts and B cells [27]. Here, we decided to investigate the ability of IL-4 to induce migration of neutrophils in vivo using the murine air pouch model. In this model, LPS is known to induce a potent acute inflammation peaking between 6–9 hours, consisting mainly in the recruitment of neutrophils (80–100%) disappearing (by a mechanism that remains unclear) after 12–24 hours [26]. Recently, using this model, we have identified that two other CD132-dependent cytokines, IL-15 and IL-21, can attract leukocytes in this model after 6–9 hours [25, 26], but unlike LPS, the response was less potent and these cytokines attract two major cell population: neutrophils (~60%) and monocytic cells (~40%). Therefore, we performed kinetic experiments from 3 hours to 24 hours. As shown in Figure 1, after 3 hours, the basal level of total leukocytes observed in control mice receiving the buffer was 0.56 ± 0.07 × 106 cells/pouch (mean ± SEM) and was not increased by IL-4, eliminating the possibility that a rapid leukocyte influx occurs at earlier time points. However, after 9 hours of treatment, the number of leukocytes attracted by IL-4 was significantly increased when compared to control (1.5 ± 0.07 × 106 for IL-4 versus 0.67 ± 0.03 × 106 cells/pouch for control). Thus IL-4 induces migration of leukocytes in vivo. As expected, the leukocyte infiltration induced by IL-4 disappears overtime, and the number of attracted leukocytes returned to the basal level after 24 hours.


Interleukin (IL)-4 induces leukocyte infiltration in vivo by an indirect mechanism.

Ratthé C, Ennaciri J, Garcês Gonçalves DM, Chiasson S, Girard D - Mediators Inflamm. (2009)

IL-4 induces inflammation in vivo. Murine air pouches were raised before injection of buffer (Ctrl) or 250 ng/ml IL-4 and exudates were harvested at the indicated periods of time and the number of leukocytes was calculated. Results are means ± SEM (n ≥ 6). *P < .05 versus Ctrl.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2742652&req=5

fig1: IL-4 induces inflammation in vivo. Murine air pouches were raised before injection of buffer (Ctrl) or 250 ng/ml IL-4 and exudates were harvested at the indicated periods of time and the number of leukocytes was calculated. Results are means ± SEM (n ≥ 6). *P < .05 versus Ctrl.
Mentions: Previous studies demonstrated that IL-4 induces chemoattraction of different cell types such as eosinophils, macrophages, fibroblasts and B cells [27]. Here, we decided to investigate the ability of IL-4 to induce migration of neutrophils in vivo using the murine air pouch model. In this model, LPS is known to induce a potent acute inflammation peaking between 6–9 hours, consisting mainly in the recruitment of neutrophils (80–100%) disappearing (by a mechanism that remains unclear) after 12–24 hours [26]. Recently, using this model, we have identified that two other CD132-dependent cytokines, IL-15 and IL-21, can attract leukocytes in this model after 6–9 hours [25, 26], but unlike LPS, the response was less potent and these cytokines attract two major cell population: neutrophils (~60%) and monocytic cells (~40%). Therefore, we performed kinetic experiments from 3 hours to 24 hours. As shown in Figure 1, after 3 hours, the basal level of total leukocytes observed in control mice receiving the buffer was 0.56 ± 0.07 × 106 cells/pouch (mean ± SEM) and was not increased by IL-4, eliminating the possibility that a rapid leukocyte influx occurs at earlier time points. However, after 9 hours of treatment, the number of leukocytes attracted by IL-4 was significantly increased when compared to control (1.5 ± 0.07 × 106 for IL-4 versus 0.67 ± 0.03 × 106 cells/pouch for control). Thus IL-4 induces migration of leukocytes in vivo. As expected, the leukocyte infiltration induced by IL-4 disappears overtime, and the number of attracted leukocytes returned to the basal level after 24 hours.

Bottom Line: The IL-4-induced expression of CCL-2 was confirmed by ELISA.Air pouch resident lining cells were harvested and were found to express IL-4Ralpha.CCL2 mRNA expression was monitored in lining cells, cells isolated from the air pouch skin, in RAW264.7 macrophage and in epithelial Mode-K cells and its expression was increased in response to IL-4 in all conditions.

View Article: PubMed Central - PubMed

Affiliation: INRS-Institut Armand-Frappier, Université du Québec, Québec, Canada.

ABSTRACT
Interleukin (IL)-4 is a cytokine known mainly for its anti-inflammatory activity. Using the in vivo murine air pouch model, we found that IL-4 significantly increased the number of leukocytes after 9 hours of treatment, consisting mainly of neutrophil (60%) and monocytic (40%) cell populations. Using an antibody array, we found that the expression of several analytes (predominantly CCL2) was increased by IL-4 before the arrival of leukocytes. The IL-4-induced expression of CCL-2 was confirmed by ELISA. Air pouch resident lining cells were harvested and were found to express IL-4Ralpha. CCL2 mRNA expression was monitored in lining cells, cells isolated from the air pouch skin, in RAW264.7 macrophage and in epithelial Mode-K cells and its expression was increased in response to IL-4 in all conditions. We conclude that IL-4 can attract leukocytes in vivo by an indirect mechanism involving the production of several analytes by, at least, resident cells.

Show MeSH
Related in: MedlinePlus