Limits...
Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages.

Joshi AD, Oak SR, Hartigan AJ, Finn WG, Kunkel SL, Duffy KE, Das A, Hogaboam CM - BMC Immunol. (2010)

Bottom Line: Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors.M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells.Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.

ABSTRACT

Background: Interleukin-33 is a member of the IL-1 cytokine family whose functions are mediated and modulated by the ST2 receptor. IL-33-ST2 expression and interactions have been explored in mouse macrophages but little is known about the effect of IL-33 on human macrophages. The expression of ST2 transcript and protein levels, and IL-33-mediated effects on M1 (i.e. classical activation) and M2 (i.e. alternative activation) chemokine marker expression in human bone marrow-derived macrophages were examined.

Results: Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors. M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells. When added to naïve macrophages alone, IL-33 directly enhanced the expression of CCL3. In combination with LPS, IL-33 blocked the expression of the M2 chemokine marker CCL18, but did not alter CCL3 expression in these naive cells. The addition of IL-33 to M1 macrophages markedly increased the expression of CCL18 above that detected in untreated M1 macrophages. Similarly, alternatively activated human macrophages treated with IL-33 exhibited enhanced expression of CCL18 and the M2 marker mannose receptor above that detected in M2 macrophages alone.

Conclusions: Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.

Show MeSH

Related in: MedlinePlus

Effect of IL-33 on human macrophage polarization. (A) CCL18 and CCL3 transcript expression in macrophages following exposure to IL-33 (10 ng/ml) alone for 24 h. (B) CCL18 and CCL3 transcript expression in human macrophages following exposure to M1 polarizing mediators + IL-33 (10 ng/ml) for 24 h. (C) CCL18 and CCL3 transcript expression in human macrophages following exposure to M2 polarizing mediators + IL-33 (10 ng/ml) for 24 h. Results are expressed as fold increase in transcript levels compared with levels of these transcripts in human macrophages exposed to media alone (i.e. control condition). Data are shown as mean ± SEM and are representative of three separate experiments with 3 donor macrophage lines. * P ≤ 0.05 compared with transcript levels in appropriate control macrophages.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2967528&req=5

Figure 5: Effect of IL-33 on human macrophage polarization. (A) CCL18 and CCL3 transcript expression in macrophages following exposure to IL-33 (10 ng/ml) alone for 24 h. (B) CCL18 and CCL3 transcript expression in human macrophages following exposure to M1 polarizing mediators + IL-33 (10 ng/ml) for 24 h. (C) CCL18 and CCL3 transcript expression in human macrophages following exposure to M2 polarizing mediators + IL-33 (10 ng/ml) for 24 h. Results are expressed as fold increase in transcript levels compared with levels of these transcripts in human macrophages exposed to media alone (i.e. control condition). Data are shown as mean ± SEM and are representative of three separate experiments with 3 donor macrophage lines. * P ≤ 0.05 compared with transcript levels in appropriate control macrophages.

Mentions: Because IL-33 had a differential effect on the expression of M1 and M2 chemokine markers in naïve macrophages, additional experiments were undertaken to explore this novel modulatory effects of IL-33 on human macrophages. As shown in Figure 5A, the addition of IL-33 alone to naïve macrophages significantly decreased the transcript expression of CCL18, while it significantly enhanced the transcript levels of CCL3 compared with transcript levels of these chemokines in untreated, naïve macrophages. When IL-33 was added with M1 polarizing mediators to macrophages, the transcript expression in these cells was dramatically shifted toward CCL18 expression; transcript levels of this chemokine were significantly increased approximately 30-fold above the M1 condition alone (i.e. control condition for this study) (Figure 5B). The addition of IL-33 to the M1 condition only modestly increased CCL3 transcript levels in these cultures. The addition of IL-33 with M2 polarizing mediators to human macrophages did not appear to skew these cells appreciably toward either CCL18 or CCL3 transcript expression since both chemokines were similarly increased above the M2 condition alone approximately 2-4 fold (Figure 5C). Thus, the addition of IL-33 to naïve macrophages favored the expression of an M1-associated chemokine marker over an M2-associated chemokine marker, but its addition to human macrophages cultured in M1 conditions promoted the expression of the M2 marker CCL18.


Interleukin-33 contributes to both M1 and M2 chemokine marker expression in human macrophages.

Joshi AD, Oak SR, Hartigan AJ, Finn WG, Kunkel SL, Duffy KE, Das A, Hogaboam CM - BMC Immunol. (2010)

Effect of IL-33 on human macrophage polarization. (A) CCL18 and CCL3 transcript expression in macrophages following exposure to IL-33 (10 ng/ml) alone for 24 h. (B) CCL18 and CCL3 transcript expression in human macrophages following exposure to M1 polarizing mediators + IL-33 (10 ng/ml) for 24 h. (C) CCL18 and CCL3 transcript expression in human macrophages following exposure to M2 polarizing mediators + IL-33 (10 ng/ml) for 24 h. Results are expressed as fold increase in transcript levels compared with levels of these transcripts in human macrophages exposed to media alone (i.e. control condition). Data are shown as mean ± SEM and are representative of three separate experiments with 3 donor macrophage lines. * P ≤ 0.05 compared with transcript levels in appropriate control macrophages.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2967528&req=5

Figure 5: Effect of IL-33 on human macrophage polarization. (A) CCL18 and CCL3 transcript expression in macrophages following exposure to IL-33 (10 ng/ml) alone for 24 h. (B) CCL18 and CCL3 transcript expression in human macrophages following exposure to M1 polarizing mediators + IL-33 (10 ng/ml) for 24 h. (C) CCL18 and CCL3 transcript expression in human macrophages following exposure to M2 polarizing mediators + IL-33 (10 ng/ml) for 24 h. Results are expressed as fold increase in transcript levels compared with levels of these transcripts in human macrophages exposed to media alone (i.e. control condition). Data are shown as mean ± SEM and are representative of three separate experiments with 3 donor macrophage lines. * P ≤ 0.05 compared with transcript levels in appropriate control macrophages.
Mentions: Because IL-33 had a differential effect on the expression of M1 and M2 chemokine markers in naïve macrophages, additional experiments were undertaken to explore this novel modulatory effects of IL-33 on human macrophages. As shown in Figure 5A, the addition of IL-33 alone to naïve macrophages significantly decreased the transcript expression of CCL18, while it significantly enhanced the transcript levels of CCL3 compared with transcript levels of these chemokines in untreated, naïve macrophages. When IL-33 was added with M1 polarizing mediators to macrophages, the transcript expression in these cells was dramatically shifted toward CCL18 expression; transcript levels of this chemokine were significantly increased approximately 30-fold above the M1 condition alone (i.e. control condition for this study) (Figure 5B). The addition of IL-33 to the M1 condition only modestly increased CCL3 transcript levels in these cultures. The addition of IL-33 with M2 polarizing mediators to human macrophages did not appear to skew these cells appreciably toward either CCL18 or CCL3 transcript expression since both chemokines were similarly increased above the M2 condition alone approximately 2-4 fold (Figure 5C). Thus, the addition of IL-33 to naïve macrophages favored the expression of an M1-associated chemokine marker over an M2-associated chemokine marker, but its addition to human macrophages cultured in M1 conditions promoted the expression of the M2 marker CCL18.

Bottom Line: Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors.M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells.Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI, USA.

ABSTRACT

Background: Interleukin-33 is a member of the IL-1 cytokine family whose functions are mediated and modulated by the ST2 receptor. IL-33-ST2 expression and interactions have been explored in mouse macrophages but little is known about the effect of IL-33 on human macrophages. The expression of ST2 transcript and protein levels, and IL-33-mediated effects on M1 (i.e. classical activation) and M2 (i.e. alternative activation) chemokine marker expression in human bone marrow-derived macrophages were examined.

Results: Human macrophages constitutively expressed the membrane-associated (i.e. ST2L) and the soluble (i.e. sST2) ST2 receptors. M2 (IL-4 + IL-13) skewing stimuli markedly increased the expression of ST2L, but neither polarizing cytokine treatment promoted the release of sST2 from these cells. When added to naïve macrophages alone, IL-33 directly enhanced the expression of CCL3. In combination with LPS, IL-33 blocked the expression of the M2 chemokine marker CCL18, but did not alter CCL3 expression in these naive cells. The addition of IL-33 to M1 macrophages markedly increased the expression of CCL18 above that detected in untreated M1 macrophages. Similarly, alternatively activated human macrophages treated with IL-33 exhibited enhanced expression of CCL18 and the M2 marker mannose receptor above that detected in M2 macrophages alone.

Conclusions: Together, these data suggest that primary responses to IL-33 in bone marrow derived human macrophages favors M1 chemokine generation while its addition to polarized human macrophages promotes or amplifies M2 chemokine expression.

Show MeSH
Related in: MedlinePlus