The difference in the levels of IL-17, IL-6, IL-1β and TNF-α (A) between SLE patients with anti-B19-VP1u IgG [VP1u (+)] and without anti-B19-VP1u IgG [VP1u (−)], and (B) between SLE patients with anti-B19-NS1 IgG [NS1 (+)] and without anti-B19-NS1 IgG [NS1(−)].

<p>Data are presented as mean ± SEM. *<i>p</i><0.05, **<i>p</i><0.01, ***<i>p</i><0.005, versus SLE patients without anti-B19-VP1u IgG or anti-B19-NS1 IgG.</p

Activity of MMP-9 and MMP-2 in lung tissue of Balb/c mice.

Activity of (A) MMP-9 and MMP-2 in lung tissue of Balb/c mice that received PBS, B19V-VP1u or HBoV-VP1u protein. Quantified results of (B) MMP-9, (C) MMP-2 and (D) ratio of MMP-9 to MMP-2. M is human serum and indicated as positive control. Similar results were observed in three repeated experiments, and * indicates a significant difference, P<0.05.</p

Lymphocyte infiltration in lung tissue of Balb/c mice.

Lung tissues from Balb/c mice that received PBS, B19V-VP1u or HBoV-VP1u protein were obtained and (A) sections of the lung tissue were stained with hematoxylin eosin. The images of lung tissue sections were magnified by 200 times. Amplified images are shown in the lower panel of each section. Lymphocyte infiltration is indicated by an arrow. (B) The number of infiltrated lymphocytes was calculated as described in the section of materials and methods. * indicates a significant difference, P<0.05.</p

Expression of MMP9 and MMP2 proteins in lung tissue of Balb/c mice.

Expression of (A) MMP-9 and MMP-2 proteins in lung tissue of Balb/c mice that received PBS, B19V-VP1u or HBoV-VP1u protein. Bars represent the relative protein amounts of (B) MMP9 and (C) MMP2 on the basis of β-actin. M is human serum and indicated as positive control. Similar results were observed in three repeated experiments, and * indicates a significant difference, P<0.05.</p

Expression of MAPK proteins in lung tissue of Balb/c mice.

Expression of (A) p-ERK, p-P38 and p-JNK proteins in lung tissue of Balb/c mice that received PBS, B19V-VP1u or HBoV-VP1u protein. Bars represent the relative protein amounts of (B) p-ERK, (C) p-38, and (D) p-JNK on the basis of β-actin. Similar results were observed in three repeated experiments, and * indicates a significant difference, P<0.05.</p

Demographic data and clinical characteristics of SLE patients with dilated cardiomyopathies (DCM) and valvular heart diseases (VHD).^a

<p>SLE: systemic lupus erythematosus; Nephritis was defined as persistent proteinuria (>0.5 g/24 hours) or pathological confirmation of renal biopsy specimens showing lupus nephritis; C3: complement 3; C4: complement 4; Anti-dsDNA: anti-double strand DNA antibody; SLEDAI: SLE disease activity index.</p>a<p>Data are presented as mean ±SD or number (percentage).</p>b<p>Include hydroxychloroquine, azathioprine, cyclophosphamide, mycophenolate mofetil or ciclosporine.</p><p>Demographic data and clinical characteristics of SLE patients with dilated cardiomyopathies (DCM) and valvular heart diseases (VHD).^{<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0113889#nt102" target="_blank">a</a>}</p

Expression of TGF-β1 and TGF-β1 receptor.

<p>Liver lysates obtained from the NZB/W F1 mice receiving PBS, NS1, VP1u or VP2 were probed with antibodies against (A) TGF-<i>β</i>1 and TGF-β1 receptor, respectively. Bars represent the relative protein quantification of (B) TGF-β1 and (C) TGF-β1 on the basis of β-actin. Serum level of (D) TGF-β1 was determined using an EIA kit. Similar results were observed in three independent experiments, and * indicates the significant difference, P<0.05.</p

Schematic illustration of the molecular mechanisms involved in the B19 NS1-induced hepatic fibrosis.

<p>B19 NS1 increases the expression of TGF-β isoforms, which elicit late activation of Smad2/3 signaling. Activated Smad2/3 cooperates with Smad4 and Sp1 to induce the expressions of fiboriss related proteins, including PAI-1 and smooth-muscle-specific (á-SMA).</p

Representative photographs of cross-sections of liver with trichrome staining.

<p>Fibrosis area (blue) in liver section from NZB/W F1 mice receiving NS1 were revealed as compared to those mice receiving PBS, VP1u or VP2, respectively. (magnification, 200). Similar results were observed in three independent experiments.</p

Activity of MMP-9 and MMP-2 and expression of IL-6 and IL-1β in lung tissue of Balb/c mice received mutated VP1u of B19V and HBoV.

Activity of (A) MMP-9 relative and MMP-2 in lung tissues of Balb/c mice received PBS, B19-VP1uD175A or HBoV-VP1uL48R protein. Lower panels reveal the ratio of MMP-9 activity relative to MMP-2 activity. Expression of (B) IL-6 and IL-1β proteins in lung tissues of Balb/c mice received PBS, B19-VP1uD175A or HBoV-VP1uL48R protein. Bars represent the relative protein amounts of IL-6 and IL-1β on the basis of β-actin. Similar results were observed in three repeated experiments, and * indicates the significant difference, P<0.05.</p