Limits...
Combustion smoke-induced inflammation in the olfactory bulb of adult rats.

Zou YY, Yuan Y, Kan EM, Lu J, Ling EA - J Neuroinflammation (2014)

Bottom Line: The results showed a significant increase in VEGF, iNOS, eNOS, nNOS, NKCC1, and GFAP expression in the bulb tissues, with corresponding increases in inflammatory cytokines and chemokines after smoke inhalation.Concurrent to this was a drastic increase in AQP4 expression and RITC permeability.This was coupled with a significant reduction in incidence of TUNEL + cells that was not altered with administration of L-NG-nitroarginine methyl ester (L-NAME).

View Article: PubMed Central - PubMed

ABSTRACT

Background: The damaging effect of combustion smoke inhalation on the lung is widely reported but information on its effects on the olfactory bulb is lacking. This study sought to determine the effects of smoke inhalation on the olfactory bulb, whose afferent input neurons in the nasal mucosa are directly exposed to external stimuli, such as smoke.

Methods: Adult male Sprague-Dawley rats were subjected to combustion smoke inhalation and sacrificed at different time points. Changes in olfactory bulb proteins including vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Na+-K+-Cl- cotransporter 1 (NKCC1), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4) were evaluated by Western blot analysis. In addition, ELISA was conducted for cytokine and chemokine levels, and double immunofluorescence labeling was carried out for GFAP/VEGF, GFAP/AQP4, NeuN/nNOS, GFAP/NKCC1, NeuN/NKCC1, GFAP/Rhodamine isothiocyanate (RITC), and transferase dUTP nick end labeling (TUNEL). Aminoguanidine was administered to determine the effects of iNOS inhibition on the targets probed after smoke inhalation.

Results: The results showed a significant increase in VEGF, iNOS, eNOS, nNOS, NKCC1, and GFAP expression in the bulb tissues, with corresponding increases in inflammatory cytokines and chemokines after smoke inhalation. Concurrent to this was a drastic increase in AQP4 expression and RITC permeability. Aminoguanidine administration decreased the expression of iNOS and RITC extravasation after smoke inhalation. This was coupled with a significant reduction in incidence of TUNEL + cells that was not altered with administration of L-NG-nitroarginine methyl ester (L-NAME).

Conclusions: These findings suggest that the upregulation of iNOS in response to smoke inhalation plays a major role in the olfactory bulb inflammatory pathophysiology, along with a concomitant increase in pro-inflammatory molecules, vascular permeability, and edema. Overall, these findings indicate that the olfactory bulb is vulnerable to smoke inhalation.

Show MeSH

Related in: MedlinePlus

Elevated cytokines and chemokines. The concentration levels of the various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF, and RANTES are increased significantly at 24 h in the SI + S group, as compared with matched controls. The increase was most substantial for IL-12, IFN-γ and TNF-α in the SI + S group, compared with the matched control. In the SI + AG group, the levels of IL-1α, IL-1β, IL-12, and TNF-α were significantly decreased compared with the SI + S group. * P <0.05; ** P <0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4197300&req=5

Fig2: Elevated cytokines and chemokines. The concentration levels of the various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF, and RANTES are increased significantly at 24 h in the SI + S group, as compared with matched controls. The increase was most substantial for IL-12, IFN-γ and TNF-α in the SI + S group, compared with the matched control. In the SI + AG group, the levels of IL-1α, IL-1β, IL-12, and TNF-α were significantly decreased compared with the SI + S group. * P <0.05; ** P <0.01.

Mentions: In the olfactory bulb tissue, the concentration levels of the cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF, and RANTES were increased significantly at 24 h in the SI + S group when compared with the matched control (Figure 2). In particular, the increase was most significant (P <0.01) for IL-12, IFN-γ, and TNF-α in the SI + S group, as compared with the matched control. Administration of aminoguanidine significantly decreased the expression levels of IL-1α, IL-1β, IL-12, and TNF-α, compared with the SI + S group at 24 h (Figure 2).Figure 2


Combustion smoke-induced inflammation in the olfactory bulb of adult rats.

Zou YY, Yuan Y, Kan EM, Lu J, Ling EA - J Neuroinflammation (2014)

Elevated cytokines and chemokines. The concentration levels of the various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF, and RANTES are increased significantly at 24 h in the SI + S group, as compared with matched controls. The increase was most substantial for IL-12, IFN-γ and TNF-α in the SI + S group, compared with the matched control. In the SI + AG group, the levels of IL-1α, IL-1β, IL-12, and TNF-α were significantly decreased compared with the SI + S group. * P <0.05; ** P <0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4197300&req=5

Fig2: Elevated cytokines and chemokines. The concentration levels of the various cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF, and RANTES are increased significantly at 24 h in the SI + S group, as compared with matched controls. The increase was most substantial for IL-12, IFN-γ and TNF-α in the SI + S group, compared with the matched control. In the SI + AG group, the levels of IL-1α, IL-1β, IL-12, and TNF-α were significantly decreased compared with the SI + S group. * P <0.05; ** P <0.01.
Mentions: In the olfactory bulb tissue, the concentration levels of the cytokines IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, IFN-γ, TNF-α, GM-CSF, and RANTES were increased significantly at 24 h in the SI + S group when compared with the matched control (Figure 2). In particular, the increase was most significant (P <0.01) for IL-12, IFN-γ, and TNF-α in the SI + S group, as compared with the matched control. Administration of aminoguanidine significantly decreased the expression levels of IL-1α, IL-1β, IL-12, and TNF-α, compared with the SI + S group at 24 h (Figure 2).Figure 2

Bottom Line: The results showed a significant increase in VEGF, iNOS, eNOS, nNOS, NKCC1, and GFAP expression in the bulb tissues, with corresponding increases in inflammatory cytokines and chemokines after smoke inhalation.Concurrent to this was a drastic increase in AQP4 expression and RITC permeability.This was coupled with a significant reduction in incidence of TUNEL + cells that was not altered with administration of L-NG-nitroarginine methyl ester (L-NAME).

View Article: PubMed Central - PubMed

ABSTRACT

Background: The damaging effect of combustion smoke inhalation on the lung is widely reported but information on its effects on the olfactory bulb is lacking. This study sought to determine the effects of smoke inhalation on the olfactory bulb, whose afferent input neurons in the nasal mucosa are directly exposed to external stimuli, such as smoke.

Methods: Adult male Sprague-Dawley rats were subjected to combustion smoke inhalation and sacrificed at different time points. Changes in olfactory bulb proteins including vascular endothelial growth factor (VEGF), inducible nitric oxide synthase (iNOS), endothelial nitric oxide synthase (eNOS), neuronal nitric oxide synthase (nNOS), Na+-K+-Cl- cotransporter 1 (NKCC1), glial fibrillary acidic protein (GFAP), and aquaporin-4 (AQP4) were evaluated by Western blot analysis. In addition, ELISA was conducted for cytokine and chemokine levels, and double immunofluorescence labeling was carried out for GFAP/VEGF, GFAP/AQP4, NeuN/nNOS, GFAP/NKCC1, NeuN/NKCC1, GFAP/Rhodamine isothiocyanate (RITC), and transferase dUTP nick end labeling (TUNEL). Aminoguanidine was administered to determine the effects of iNOS inhibition on the targets probed after smoke inhalation.

Results: The results showed a significant increase in VEGF, iNOS, eNOS, nNOS, NKCC1, and GFAP expression in the bulb tissues, with corresponding increases in inflammatory cytokines and chemokines after smoke inhalation. Concurrent to this was a drastic increase in AQP4 expression and RITC permeability. Aminoguanidine administration decreased the expression of iNOS and RITC extravasation after smoke inhalation. This was coupled with a significant reduction in incidence of TUNEL + cells that was not altered with administration of L-NG-nitroarginine methyl ester (L-NAME).

Conclusions: These findings suggest that the upregulation of iNOS in response to smoke inhalation plays a major role in the olfactory bulb inflammatory pathophysiology, along with a concomitant increase in pro-inflammatory molecules, vascular permeability, and edema. Overall, these findings indicate that the olfactory bulb is vulnerable to smoke inhalation.

Show MeSH
Related in: MedlinePlus