The effects of particulate matter on inflammation of respiratory system: Differences between male and female.
Air pollution is known to exacerbate respiratory diseases and epidemiological studies have shown that women present more chronic respiratory symptoms than man exposed to traffic pollution, however, the reason why is unclear. This study evaluated the inflammatory differences in BALB/c mouse males (n=34) and females (n=111) in three phases of the estrous cycle that were exposed to ambient air (AA) or concentrated ambient particles (CAPs). Tracheal hyperreactivity to methacholine, bronchoalveolar lavage fluid (BALF) and immunohistochemical of airways and lung parenchyma were studied. Hyperreactivity increased in CAPs-exposed female mice compared with AA-exposed mice in estrus (p<0.05) and proestrus phases (p<0.05) and decreased in CAPs-exposed males compared with those exposed to AA (p<0.05). Males had increased numbers of total cells (p=0.037) and macrophages (p=0.028) compared to females. BALF levels of cyclooxygenase-2(COX-2) (p=0.000), transforming growth factor alpha (TGF-α) (p=0.001) and IL-8 receptor alpha (IL-8Rα) (p=0.014) were increased in males compared with proestrus, estrus and diestrus females, independent of exposure. Proestrus females exhibited significantly higher cadherin expression in lung parenchyma than did males (p=0.005). CAPs exposure increased matrix metalloproteinase-9 (MMP-9) (p=0.024) and isoprostane (p=0.003) expression in the airways of both, males and females. The level of substance P (SP) (p=0.001) increased in lung parenchyma in males compared with females, while IL-17 levels in airways (p=0.042) and in lung parenchyma (p=0.008) increased in females. MMP-9 levels (p=0.024) were significantly lower in the lung parenchyma of CAPs-exposed females. TGF-α (p=0.007) levels increased in the lung parenchyma of CAPs-exposed females compared to AA-exposed females. These results suggest that inflammatory markers differentially expressed in male mice were mostly linked to acute inflammation (IL-1β, IL-8Rα, COX-2), whereas in females, markers that may lead to a chronic inflammatory process such as IL-17 and remodeling (MMP-9) were increased.
Department of Pathology, Experimental Air Pollution Laboratory, LIM05 - School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: kellyyos@usp.br.
Kelly
K
Yoshizaki
Department of Pathology, Experimental Air Pollution Laboratory, LIM05 - School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: josemarabrito@yahoo.com.br.
Jôse Mára
JM
Brito
Department of Pathology, Experimental Air Pollution Laboratory, LIM05 - School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: burns@usp.br.
Luiz Fernando
LF
Silva
Post Graduate Program in Biophotonics Applied to Health Sciences, University Nove de Julho (UNINOVE), Sao Paulo, Sao Paulo, Brazil. Electronic address: alsantosfranco@gmail.com.
Adriana
A
Lino-Dos-Santos-Franco
Department of Pathology, Experimental Air Pollution Laboratory, LIM05 - School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: danperronifrias@gmail.com.
Daniela Perroni
DP
Frias
Department of Pathology, University of West Paulista - (UNOESTE), Presidente Prudente, Sao Paulo, Brazil. Electronic address: renata@unoeste.br.
Renata Calciolari Rossi
RCR
E Silva
Department of Pathology, Experimental Air Pollution Laboratory, LIM05 - School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: luisfamato@usp.br.
Luís Fernando
LF
Amato-Lourenço
Department of Pathology, Experimental Air Pollution Laboratory, LIM05 - School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: pepino@usp.br.
Paulo Hilário Nascimento
PHN
Saldiva
Experimental Therapeutics Laboratory, Department of Medicine, School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: iolanda@calvo.com.pt.
Iolanda
I
de Fátima Lopes Calvo Tibério
Department of Pathology, Experimental Air Pollution Laboratory, LIM05 - School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: tmauad@usp.br.
Thais
T
Mauad
Department of Pathology, Experimental Air Pollution Laboratory, LIM05 - School of Medicine, University of Sao Paulo, Sao Paulo, Sao Paulo, Brazil. Electronic address: mariangela.macchione@fm.usp.br.
Mariangela
M
Macchione
D000397:Air Pollution / Q000009:adverse effects*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D016207:Cytokines / Q000378:metabolism; D005260:Female; D007249:Inflammation; D008168:Lung / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D052638:Particulate Matter / Q000009:adverse effects*; D012737:Sex Factors
D016207:Cytokines; D052638:Particulate Matter
Air pollution; Cytokines; Inflammation; Lung parenchyma; Metalloproteinase; Neurokinins