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Table 3 Review of reported effects on inflammatory cascade in varying skin models upon exposure to PM

From: Impact of airborne particulate matter on skin: a systematic review from epidemiology to in vitro studies

Model PM type Dose and application Exposure time Main findings Ref.
Ex vivo human skin SRM® 1649b 2 mg/cm2, topical 24 h - Increased MMP-1 protein expression. [119]
Mice, BALB/c SRM® 1649b 100 μg/m2, topical 24 h repetitive exposure, 5 d total - Increased COX2 protein expression. [122]
SRM® 1649b 100 μg/cm2, topical 24 h repetitive exposure, 5 d total - Increased epidermal thickness.
- Neutrophil infiltration.
- Increased COX2 protein expression.
[179]
Mice, BALB/c with disrupted barrier PM ≤1 μm from Seoul, Korea 8 μg/cm2, topical 6 h and 2 w repetitive exposures, 10 times in total - Increased epidermal thickness in both skin types.
- Neutrophil infiltration.
- Increased mRNA expression of IL-8 functional homologs (KC, MIP2, LIX).
- Increased mRNA expression MMP13.
[121]
Mice, NC/Nga, AE model The soluble phase of DEP. 1 mg/time, topical Repetitive exposure, every 1, 3, or 9 weeks in total - Increased AE lesion formation.
- Increased total IgE levels.
[226]
Mice, HR-1 SRM® 1650b 100 μg/mL, topical 7 d - Increased epidermal thickness. [124]
SRM® 1650b 100 μg/mL, topical 7 d - Increased epidermal thickness. [168]
SRM® 1650b 100 μg/mL, topical 7 d - Increased IL-1β and IL-6 protein expression.
- Increased TLR5 protein expression.
- Increased MyD88 protein expression.
- Increased phosphorylation of p65.
[169]
HSE SRM® 2975 200 μg/mL, systemic Every 2 d, 6 d total - Decreased IL-8, CXCL10, and ICAM1 protein secretion. [125]
HEE CAPs, PM2.5 0.5 and 2.0 μg/cm2, topical 24 and 48 h - Nuclear translocation of p65.
- Increased IL-1α protein secretion.
- Increased COX2 protein expression.
[128]
CRM no. 28 25 mg, topical 6 and 24 h - Upregulated mRNA expression of IL1A, IL1B, IL6, CXCL8, CCL20, MMP1, MMP3, MMP9, MMP12, and ICAM1 after 6 h.
- Downregulated expression of tissue inhibitors of MMPs (2–4) after 6 h.
- Induced IL-8 and MMP-1 protein secretion after 24 h.
[129]
PM0.3–2.5 from Benin, West-Africa 15 and 30 μg/cm2, topical 24 h - Increased IL-1α and IL-8 protein secretion.
- Increased MMP-1 and MMP-3 protein expression.
[133]
PM2.5 from Seoul, Korea 50 μg/mL, topical 24 h - Increased MMP-1 protein expression. [132]
SRM® 1648a 2.2, 8.9, and 17.9 μg/cm2, topical 24 and 48 h - Increased IL-1α protein secretion. [131]
NHDF SRM® 1649b 100–400 μg/mL, systemic 24 h - Phosphorylation of ERK and JNK.
- Increased MMP1 mRNA and protein expression.
[172]
Diesel PM 30 and 60 μg/mL, systemic 24 h - Increased MMP3 and MMP9 mRNA expression. [138]
SRM® 1649b 50 μg/mL, systemic 24 h - Increased MMP1 mRNA expression. [119]
SRM® 2787 30 μg/cm2, systemic 24 h - Increased IL-6 and IL-8 protein secretion.
- Increased MMP-1 and decreased procollagen and TGF-β protein secretion.
- Increased IL1B, IL6, CXCL8, and IL33 mRNA expression.
- Increased MMP1 and MMP3 and decreased TGFB, collagen type I alpha 1 chain, collagen type I alpha 2 chain, and elastin mRNA expression.
[135]
ERM-CZ100 200 μg/mL, systemic 24 h - Increased MMP-1, −2,-8, −9, −13 protein expression.
- Nuclear translocation of p65.
- Phosphorylation of ERK, JNK, and p38.
[136]
The pre-conditioned medium of HaCaT treated with CRM no. 28 125 μg/mL, systemic 30 m, 48 h post-incubation - Increased PGE2, TNF-α, IL-1β, and IL-6 protein secretion.
- Increased COX2 protein expression.
- Nuclear translocation of p65.
- Phosphorylation of p38, ERK, and JNK.
- Increased MMP-1 and MMP-2 protein expression.
[137]
Diesel PM 30 and 60 μg/mL, systemic 6 h - Increased MMP2 and MMP9 mRNA expression. [227]
NHDF and HaCaT co-culture SRM® 1648a and SRM® 1649b 50 μg/cm2, systemic 24 h - Phosphorylation of p38.
- Increased IL1A, IL1B, IL6, and CXCL8 mRNA expression and protein secretion (HaCaT).
- No changes in TNF mRNA expression and protein secretion (HaCaT).
- Increased MMP1 and COX2 mRNA expression (NHDF).
[178]
NHEK PM2.5 from Xi’an, China 50 μg/mL, systemic 24 h - Top upregulated genes from transcriptomics analysis are CXCL1, IL1A, and IL1B. [134]
Diesel PM 30 and 60 μg/mL, systemic 24 h - Increased IL1A, IL6, CXCL8, and TNF mRNA expression and protein secretion. [138]
ERM-CZ120 3, 10, 30 and 100 μg/mL, systemic 24 and 48 h - Increased IL1B, IL6, CXCL8, and TNF mRNA expression after 24 h.
- Increased IL-1β, IL-6, IL-8, and TNF-α protein secretion after 48 h.
- Increased MMP1 mRNA expression and protein secretion after 24 h.
[173]
SRM® 1650b Unknown 24 h - Increased IL-1β and IL6 protein secretion.
- Increased IL-6 protein expression.
[169]
PM ≤1 μm from Seoul, Korea 40 μg/cm2, systemic 24 h - Increased CXCL8 mRNA expression and protein secretion.
- Increased MMP1 mRNA expression and protein secretion.
[121]
SRM® 2786 1 mg/mL, systemic 6 h - RNA-Seq analysis: Upregulation of IL1B, IL36G, CXCL3, CXCL8, and IL1R2. Downregulation of MMP3 and MMP28. [141]
SRM® 1649b 50 μg/cm2, systemic 24 h - Increased COX2 protein expression. [181]
SRM® 1649b 100 μg/mL, systemic 24 and 48 h - Increased IL-8 protein secretion. [228]
Diesel PM 20 μg/mL, systemic 48 h - Increased IL-1β and IL-8 protein secretion. [229]
Diesel PM 30 and 60 μg/mL, systemic 6 h - Increased IL1A, IL6, CXCL8, and TNF mRNA expression. [227]
Asian dust storm particles from Seoul, Korea 25 μg/mL, systemic 24 h - Increased IL6, CXCL8, and CSF2 mRNA expression.
- No changes in IL1B, IFNG, and IL18 mRNA expression.
[139]
PM2.5 from Seoul, Korea 25 μg/mL, systemic 24 h - Top upregulated genes from transcriptomics analysis are IL1B, IL36G, IL1A, IL1R2, PTGS2, IRAK2, MMP1, MMP9, and MMP10.
- Downregulated gene is CXCL14.
- Induced IL-1α protein secretion.
- Phosphorylation of p65 and p38.
[132]
HaCaT CRM no. 28 125 μg/mL, systemic 30 m, 48 h post-incubation - Increased PGE2, TNF-α, IL-1β, and IL6 protein secretion.
- Increased COX2 protein expression.
- Nuclear translocation of p65.
- Phosphorylation of p38, ERK, and JNK.
- Increased MMP-1 and MMP-2 protein expression.
[137]
PM2.5 from Shanghai, China 10–100 μg/mL, systemic 24 h - No changes in CSF2 protein secretion.
- Increased TSLP, TNF-α, IL-1α, and IL-8 protein secretion.
[144]
SRM® 1648a 50–200 ppm, systemic 24 and 48 h - Increased TRPV1 mRNA and protein expression (via p38/MAPK and NF-κB pathway).
- Increased IL-1β, IL-8, and TNF-α protein secretion.
[130]
SRM® 1648a and SRM® 1649b 50 μg/cm2, systemic 24 h - Induced phosphorylation of p-38. [178]
SRM® 1649b 50 μg/cm2, systemic 6 and 24 h - Increased phosphorylation of ERK, p38, JNK, and Akt after 6 h.
- Increased COX2, ICAM1, cPLA2, and PGE2 protein expression after 24 h.
- Increased MMP-9 protein expression after 24 h.
[143]
SRM® 1649b 50 μg/cm2, systemic 2 and 6 h - Increased COX2 and MMP-9 protein expression.
- Phosphorylation of ERK, JNK, and p38.
[142]
SRM® 1649b 25 and 50 μg/cm2, systemic 4 and 24 h - Increased COX2 protein expression.
- Increased PGE2 and IL-6 protein secretion.
- No changes in IL-24, IL-1β, and TNF-α protein secretion.
[122]
SRM® 1649b 25–100 μg/cm2, systemic 4 and 24 h - Increased COX2 protein (24 h) and mRNA (6 h) expression.
- Increased PGE2 protein secretion after 24 h.
- Nuclear translocation p65 after 4 h.
- Phosphorylation of ERK, JNK, and p38 after 4 h.
[179]
SRM® 1649b 25 μg/mL, systemic 2 and 24 h - Increased IL-6, IL-1β, and IL-1α protein secretion, and mRNA expression.
- Phosphorylation of p38 and AP-1.
[180]
SRM® 1649b 50 μg/mL, systemic UK - Increased protein expression of COX2, PLA2, ICAM1, and MMP-9.
- Phosphorylation of ERK, p38, and JNK.
[230]
SRM® 1649b 50 μg/cm2, systemic 6 and 24 h - Increased COX2 protein (24 h) and mRNA (6 h) expression.
- Increased PGE2 protein secretion.
- Phosphorylation of p38, ERK, JNK, and p65.
[181]
SRM® 1649b 100–400 μg/mL, systemic 24 h - Phosphorylation of ERK and JNK.
- Increased MMP1 mRNA and protein expression.
[172]
SRM® 1650b Unknown 1 h - Binding of PM to TLR5. [169]
SRM® 1650b 50 μg/mL, systemic 24 h - Induced phosphorylation of ERK, p38, and JNK. [182]
SRM® 1650b Unknown 3 h - Increased IL-1β, IL-6, IL-8, IL-16, and TGF-β2 protein secretion.
- Increased IL6 mRNA expression.
[169]
SRM® 1650b Unknown 24–72 h - Increased IL-1β, IL-6, IL-8, IL-16, and TGF-β2 protein secretion.
- Increased IL-6 protein expression (time-dependent increase).
- Increased IL6 mRNA expression.
- Increased TLR5 protein and mRNA expression.
- Increased MyD88 protein expression.
- Nuclear translocation of p65.
- NOX4-TLR5 interaction.
[169]
SRM® 1650b 50 μg/mL, systemic 24 h - Phosphorylation of ERK, JNK, and p38. [168]
SRM® 1650b 50 μg/mL, systemic 30 m, 1 h, and 24 h - Increased MMP-1 protein activity, expression, and mRNA expression.
- Increased MMP-2 and MMP-9 protein expression.
- Activation of the MAPK pathway.
- AP-1 binding to MMP-1 promotor.
[185]
SRM® 2975 100 and 200 μg/mL, systemic 30 m and 24 h - Decreased IL-8 and CXCL10 protein secretion after 24 h.
- Phosphorylation of p38, ERK, and JNK after 30 min.
[125]
CAPs, PM2.5 5–25 μg/mL, systemic 1, 3, 6 and 24 h - Nuclear translocation of p65.
- Increased IL-1α protein secretion.
[145]
CRM no. 28 125 μg/mL, systemic 30 m, 24 h post-incubation - Nuclear translocation of p65.
- Phosphorylation of p38, ERK, and JNK.
- Increased PGE2, TNF-α, and IL-6 protein secretion.
- Increased COX2 protein expression.
[137]
CRM no. 28 125 μg/mL, systemic 30 m, 24 h post-incubation - Nuclear translocation of p65.
- Phosphorylation of p38.
- Increased COX2 protein expression.
- Increased PGE2, IL-6, TNF-α, and IL-1β protein secretion.
[231]
ERM-CZ100 and ERM-CZ120 100 μg/mL, systemic 24 h - Increased IL-1β, PGE2, and IL-6 protein secretion.
- Increased COX2 protein expression.
[232]
ERM-CZ120 100–400 μg/mL, systemic 24 and 48 h - Increased PGE2 protein secretion. [126]
HEK-001 SRM® 1650b Unknown 24 h - Increased IL-1β and IL-6 protein secretion.
- Increased IL-6 protein expression.
[169]
JB6 P+, mouse cell line SRM® 1975 10–20 μg/mL, systemic 12, 24, 36, and 48 h - Activation of NF-κB.
- No activation of AP-1.
- Activation of the Akt/PI3K pathway.
- Phosphorylation of ERK, not of p38 and JNK.
[233]
  1. Abbreviations: h, hour; d, day; HSE, human skin equivalent; HEE, human epidermal equivalent; NHEK, normal human epidermal keratinocyte; SRM, standard reference material; PM, particulate matter; CAP, concentrated ambient particles; ppm, parts per million; CRM, certified reference material; CXCL10, C-X-C motif chemokine ligand 10; TLR, Toll-like receptor; IL, interleukin; MAPK, mitogen-activated protein kinase; TNF, tumor necrosis factor; MMP, matrix metalloprotease; NF-κB, nuclear factor kappa B; PGE2, prostaglandin E2; AP-1, adaptor protein 1